bo.e. - shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/16466/10/10_discussion.pdf ·...
TRANSCRIPT
DISOUSSIoa I
Adult __ allm 11., .. r.pp ••• ntl a 0 ... 1,
bo.,ge:DOuland I' .... 'log poat-alto'10 cell population
.,.t.a. Sur8lcal or ch.-1oal .blatlon of • al ••• ble
portion ot t.bl. oraAD would .11cl~ r ••• a ... ,l •••• t191.,.
A •• ttar ... ,., control tl •• ue analoa- to '\PIOJ' • .., b. found in r ...... tlq 11'1er. Tble 'leau. ha •• "rapid
8I'Ofth •• te ftloh. bo.e._ I: .toPI att. 8-3 .... .
Web .. and c.' .. o tles,.) repol"'ecl that the ..... r.'10D
of 11.er .... an4 it. CODa,t.ent. 1 .... leebla. a' •• _ and reproduelble. fble ppolU".'1rta cell POpul •• l0D
of ll •• t- I, Ia:tOWIl '0 be 't'Uln.,.abla to tbe a.'loll or obea1oal oarclDosene. Velna thl.. _d.l ..... pr ••• n'
1D .... tlsaUcm baa l'aoorcl4Kl the 'blo~loal obuS.' el101'ed bJ nreA. Alao It re.or4. the S.ntlu-.oe of
o.r'alD ehe-'eal .o41t~ 11k. .PG. ..carblo ac14 .nd
e.~a4lol em. the blocb..s.cal obana' • .ut01 , .. bJ DlBA
la til. I"q ..... ,1D& 11 .... of -" •••
sev..--.1 .~41 •• baY. ab-e.4, b.en dOfte Oil .. ,..
l1I'of11.. 1ft ... .mtI'.'I.. ..aoa • .roue aa4 _ .. oerow. it.,.,.. ..,. •• of oarbob,.., ... ,.boll ..... .,.,1 _.4184 1ft tu.os-oue. blat DOt lD Pl'.omearoue. 11 •••
219
It 1. • ... 14.ft' tro. the 4at. (fabl.. 1-8) that
ltodJ •• lp, 1. u.ua11, deer ••• ed 10 etltt •• at lI'oup. ot
&Dial.. !he 4" ...... 1n th. boq •• 1Ih' att. aura • ., anet att.,. a4JIlnl.tr.'loD of 4ltt __ .t obtaloal. appear.
to be becaua. ot plqalo1ogloal .ve •• , .. It 1. a ... r~lJ notic.d that after operatton, the lJUbJeot eatt ... tl'Oll
tr •• lent anorexia whloh ultllsatGJ re.ult_ 1A •
re4uoUoJl of the bo4,. .es.p.t. Art lDor .... at 8 br 1a
,be bod, •• lsh' 111 8'0 aa4 DJlBA tr •• t" poup ..... \0
b. an'ascDl.tlc .ttec' ot the two ohe1'l10&1 ••
ChIlDS •• 1a 11 ... er nlpt .t •• 10'1. ta ... ala attar par'lal h.p.tecto., are ••• lD Tabl. '7 an4 ..
reooret an IftP.... 1ft 11... ..iaht 0Dl7 at 2" bit .04 not
betore th.t. Th1. las period ot 11 ... .,. ... labt laor ••••
c1l1'.o'l,J correlate. with \be Wtta1 prep .. atl •• period
of iliA blollJntheal. whloh 1. about 14 .. atter aurlerJ
(Sillelt .!!. a1.. lQee ). Brown and Zaaala'" (lQ,'1) el.o
"POJ'ted • p'a411al in...... 1n 11 .... 1' •• 1p' att.r aura..,· 8lallar 1110"' .... 111 11 ••••• lab' h.a al80 b.eD .•• POl"h4
bJ Vob.1J ... and bi. oowozaket-. (1 iSS) who ....... 4 ~.,
tbe 1ft ...... 1l'l 11 ... er .. ISb •• ., b. atvlttut." - th.
11101' •••• 4 ....,.,. an4 .1 .. of *1 •• uba.q\lent 1;0 part.1N.
ablation ot 15..... It k .. alao -- "eport" 'ba' tor the tlra' 2. hi' at,,, aurS."", ,bel". 1. DO 1Dcr._
in the i\uJlber ot 01111 .......... pI4 In ..... .
220
10 t.he al •• or t.ha 11" .. ft'agant 4ue to •• 11ul. ..
bJPeI'lroph., ba. hen taklna place (BJtuea!1.!l:.. l~aa). Pr08 ~.t '1 •• on, DUaber ot oella t.ncr ... ed ~ap1cUJ
(1 ••• bJpepl •• la). OUP r •• ulta ... Sa a_eral ..... _t w1tb the rewt. ot the •• _thor. ad ...
alao ooaalahn' wltb the 8. __ &1 CODamaua tha' alto!S.
41 vi. loa 1. Dob .tto.able 4uttlng tbe t ..... , bouPa of
r •• toration. Our ... aulta 1Il ... sen ... tlf18 11 ... are well.
auppo~'" '" tbe ..... &tlon8 ot UD'J r ••• a1"cher. who
noted • .1sn1tloant lncr.... 1n the liver •• 1abt att .. partial hepateatoaJ (~e. at a1.. 19., Ro.lkott aD4 --Pot ..... lot8, W.b. and Cantero, 106'., ••• 111e.!!.!L.,
18"10, 8.'-own and ZaaallkJ, 1 vn). Ho ...... ,iarkrl." (lDle) 41d DOt tlDd an in ••••• lzl tbe 11._ .elab'
at,,, partial r ••• 'loD 1n r.ta. D.A wbeD Sl ... k
the _laal. wttb reSeDer.tlna l1ye .. oau •••• a_na ••
In 11... ..lght a' 18. ae and ?e tar and we ••• tba,
the 11'1. ..lab' ot thi. FOUP ot ... S.al ell.pl&., •
.-1" •• 1 ••• the tha' ob • .-.e4 1n ab ... opel'at.4 claal. (\fable 9). 'Ibis ".or .... in 11..... wa1aht ..,
" 'bee&11.. of the 4.0.-••• 14 rat. of DlIA bloqntb..s.a aD4 th .. _", d.o ..... eet .. at. of cell 41 .. 1.1on 1DdUOM
_ DJlBA III r.g ..... '1na liver (lubD' an4 Pro41. 1981,
."~"UIJld.' an4 PbUlpa, Uf"lOJ Db1_. unpubl1abe4 work).
221
I, UtIO ..... 'bat DtmA ba. Snbibl ted b".trophio
aottdt, 1ft the 11yer. _PO alao Saduo •• the 11 ...
•• 1pt (Tabla 8 and Plgure &) .s.~ .. wbea 61Yen alone
OJ' .baD 61yOft e10ft8 with OIlSA. With the a.allable 4a' ••
It 1. 41ttleul' to • ., bow an4 wb7 40.. 110 ra4l1Ca the ,
11"e!' welSht but •• obaOl"YfJ that .PO 40ea DOt ... aUf
slp1tloaDtl,. al' .. *. DMBA-1D4uoed chan,_. SIl
~.8.ner.t1Dl liver •• 1~'.
a.o01'bl0 8014 alao brought about • decr.... ta 11 ...... 1Sbt lr1 anS. .. l. _b~.o'ed to par'tal bep.,.ot.,
('..,1. 9 and "1gur •• ). The 11.er welght ot ,bla croup
1. 1 ••• the that of ah ... operattcl control. a' all th41
intervale. It 1. or tnt .... , to not. tbat in 001I1>lr1.'1oa
.1'" DUBA, aaeorbl0 aold enhano •• the 11 ..... lab' iD! tlall,. u4 thM the •• llbt .a. tOlla4 to b. 1... iSba
that or ~'1a11, bepat •• '-l •• d control. It s.a po •• lble tha' ,,001'b10 ao14 J!!£..!!. pl.,8 ~l • .t.oblblto17
aotioa beto.. It .e' •• ,.bolt.ad. fhtm.' 1.' •• lnter.,al.. tbe ettact or DMBA 1. predo_t.aant.
AD iD...... ill tt. 11 •••• lgb' at,.. ..vacllol
a4adnlatr.'lon (Table 10 and lIlaw. "I) oould b. ctu '0 It. ..... aoouaul.'1n& prop-tJ. A .1.1110 •• J.Qore_ 1. -1nl'J ob .... a4 at peak bo\lr. of _toale ,_up the
222
we1ah' •• abed blp_ ~pout the ob ...... tloa
pel"lod tban -. .. , 1ft pu'l.U, hep.'eotoll1se4 auSIIala
(01. Tabl. 9). A .sail.,.. bor.... 1n 11, ... 1n ••• J.cb' at.. • .... 101 adatDl.t.aUon t. ob .... e4 cl\1Irlq tba
eMulns • lIP .blob .., b. reoopla.a wltbla • b1' at,_ the adalftl.tratloa (PP1.4_. 1916). II) ,he pr ••••
laY •• ttla'lon 81ao. lDor.... 1. ",talbla .100. 8 bP at ... • alai.watloft .1'b. Snor •••• lD 11 ..... lab- .., ... ~11lO1pa1lJ b. 4. to .C~.'10D ot oraml0 •• , .. 1al
wbloh r.aobe4 '0 1t. aulauJl Sa abouS .8 .. aad ..,
alao be aocou'" tor '" aD lnor .... Sa w.t.. .. e1 .... o1r •• oon,_t_ 80 ...... , lAooablD4lilcm .1* DlDl (tab1. 10 and Flgur. '). an laOr •••• 1a 11.0
.. llh' 1. oba ... ed cml, ., 8 all4 18 .. an4theD ...
•• 1abt 1. tClUDd to be redu.oe4 .tpU1o .. 'lJ •• 26 ..
an4 ther.at, .. r ... 1M4 lower _. th., of par'laU.,
hepateotoa1.- oontrol.. •• OtlD 01 ... 1, aotl •• tbat
•• VOS- 1. not .ob ert.'l.. 1Jl alt..-iDa DMBA-lr.u1uc-
4.ore... in l1y.r .elBb'.
OW.,.leot;o.,. •• asp .. ' ..... N ,. 1ft • 4 ......
1ft 11" .... 1&h'. In o(Mlb1aatlon with DraA. \b. 4eor-.
1ft 11" .... lab' app .... to b. o~.tl" • • tteo' of \h.
two tr •• ' .... 'Tabl. 11 aD4 'laVe 8). SO ••• -,'"
••• ..,.01 I.. sly. to t'bta •• o •• leoMlda.a.perUa111
223
hep.'eo~II1Md m1aal.. 1t oou14 not .. a.tor. the
4.,,, .. _ 11 ..... l&h' Wo\lCh' about bf oyerleoto.,.
It 1. lntere.tlq k 110M t'bat In DeA ira.ted partlall,
bep.teotoatae4 ulaal. (Table 18 an4 'lav. 8), tile
•• 1ght ... !acr ... eel bJ about. 28 per oell' or ooaWol
yaw. tlll't.u, a' e ~. Tbi. 1Ilore... IPpeare to .. the -t-&oDlatl0 .rtM' of DMBA and ..... 101. Sa till.
croup. the al •• do •• of •• tra4lol doe. 1'1.0\ app ... to
be ettaott". 011 DM1lA 1a4uoe4 em .. e. and allKl that of
o ....... leotollJ •
lA th. pr ••• t lfty •• 't •• 'l.. • • __ al lftGr ....
III D _'I .. 't, I,DO,lo" aft .. par'lal Iutpat .. ioIIJ (table 13). 1ao.,at.o •• tSaatlona or HK .ow that ....
1. alao •• 1p1tloant lftore ••• lD au _4 BIll (fabl. It
aD4 26), ln01"' .... 1ft BIll belD1 lDor ..... Co INCh .or. thaD th., 1a BlU. fable a1 abo •• Ul.' ~ l\1p .. U
aottYlt, 1. r4l4uc_ as.pUloaaU,. 'lb ...... a1 Sao .......
In low IDa BIt' .upport. _ lnor .... , .a'. 01 alJ001,.,.. lD the 41y1411lS oell. "l&,_-.!l &1., le", ... .!!.!'&A. 1~'6). ".. r • .w. t. ... 10 11De w1th ~ •• of 8ato aM bJ.. 00.,1'11.-. (ltet) wbo ob, .. .,_ aD lrlol' ....
SA BK (low Ita) aDd cleo ...... ill OJ{ (hlP Ka). !tala
224
p.i'.,.D of D .0'. yl" 1. a1a11111' to that of bep&t1oII ••
or ditterefit srowtb r.t.. (Sbat~ll.!l Al.v 1981) ... OK -opp_ to • ..,.., 10. l .. ti and alao • ." auob aSa1lu
'0 ..... , of feCal 11"81" .... a teUle lao.,.. If I.e.
Glt baD4 1. pr...... tbe otbe.. belna pr.poact8Jlan'.
, .. 111a .!l.!L. (1988) &1.0 toUD4 • .11111.. pa"eftl Sa
........ ,Sfta 11... or .. at_
w. kDo. that "'-S .... t1Qg 11._ 1 .... of the
.'lawee with b18bea' al~10 aotlvit, an4 oae b. 0 .....
with • 11.... tuJlOJ!t and ther.tor. the pr •• aIlO. of ..
• s..u.. pattern or BE leo.,... Ie DO' ... , ..... 11o .. " •• KDox and bia o01lOl"'~a (1170) JOinted o.
th., altboUCh f.tal aD4 p.a.-.tina 11 .... &row ..
t .. , •• the t •• , •• , srotr1D& hap.to... their BI ooa .....
• ·.'1ODa ar. auoh low .... tharl 111 tbH. ,..... ou. r.8Ultta ... la pod .... _., with tbo •• or Sbaru
!!..!l£ (186&). SJdow and _dow (191&" Jacob (1"8)
an4 x. • .!l!A.t.. (1010). Proa the atwSl •• of z..a ...
hie •• .oolat.. (lt90). l' .pp .... tha, the ... _,1_ o~ 1.0.,1&10 1IOd1l1 •• '10J'1 1A rea .... 'lna 11 ...... _ ....
OOJItrOY ... lal. bu' 1, .... that the d ...... 1ft srow-•• ,_ SA iMp ..... 1. DO' aooapaale4 '" the .... to •• 'l_
of (lX ._1n" ad a1_ .. , ther. 1. flO _we1.'S.onahlp
lD r.' .... 'lIIC 11.... between tbe deer.... Sa ld.a'b .. OX anct lnOJt .... Sa low IDa IIX.
225
A d .. r.... 1ft OK le.el .tab' oa",. • alo ....
• '111 •• 'lOft ot a1\&00 •• bJ 11..-er at,...t_ 1Dtaa of
oarbohJdrah anel .1 ..... 10ll ot blood -UC- OOftceDtr.slOJl.
"'Lean and. !Irown (1966) a\l68_.'.4 that obe, •• 1D ..
of ~. HI lA_I.,. DO' ODlJ tho 10" of tb4t: blp .. GK
ht al.a • -anae In III or the .~ .1~ sluo •• _, 10. OOftoefttratlcma to • value ... tlYe '0 .1&ht tlua
\be ........ toP aOftlal rate l1ye!' U. Ocnwer •• 1J. total bor.... 1D B& .., 1... ~ ..... \1t1.11 .. '108 or 81uoo •• 71el4lD& • gre.t .. ooncatr."lon of &1\100 • .-&-
pboapbat. bJ the aaalD ox14atl". l'Gut... ft •••• lU41 ..
... tur ... ooDtlrae4 bJ ueot:ropbol'.tio .tu41 •• of
Oou81 •• aDd M, •• 1001., •• (1ge.).
!'abl. &'1 Uluaw.t .... , lbe Ift4 k4' .., .. of
811001,.1 ... ,n I.. aleo bO ...... at,. p .. 'l.-1 bap.'''toItJ att .. an Wtlal 4eoreu.. ITarioua 1rrf •• 'laaUou ba ••
lIbon tha' lnt.llaUlo.,loD ot .1,001,.1.18 aoooap&Dl.,
'" 0.0 mor .... 1ft PPI' _,1.1_. In anwlaa ... , 11., ..
euaor. (Shonk.t! ,ale. 1 ila, 1D0:a.. 1 ge,) aM lD tull
poe bepa"'. (DaDa •• , ".!l:u 18'72, 10-'4) alao. u t.ncs ..... In PH aotlvlt)- ft._'10ed. ob ..... tlODa of
l\ubeneld.ok (18"1.) .uppo", 0\11" 1" •• u1.t ... all initial
4eo .... e 10 ,PIt ao",91" ..,. po •• l'blJ be cl1.l. so ,-
226
4........ attlll1t7 of ,.,1 to It •• ub .... '. wlhtob 1.", on lDor...... Alao 1D tu.or. of --oJ sl.M (n.abpaad.
at ~., 1~'7). -.40 •• , .. 1_ aM o ... tx (Lauro ••• , al •• -_ .. 19'14, "" .. .,0,1876, ..... ball e' &1., lVts) ami· of aueov.a lIttIlbra... of coloD aa4 reo'_ (8rlab4 .114
Pl.obeP .... , 1eva) aD ID ....... ,Pll 1 ... 1 1. ob ..... 4.
Ho ...... , lewr_i. patld'. aPe .. eport. to baYe DOJIIIal
le.l1 or ,n: and JIlt 1n tbelP lou.ale 1.ukOOJ'~"
(MaJan .!..\.!lu 1989).
"l'1lY.'. lela... also showe aD lDOI" ••• " 1.Y~ of aotl.1" at .... par'lal up., .. .., (~abl. 43). IlaU_
.... ult. ba"l hen put tor'b 'bJ 1Ud • .!l'& (11?2) a.
Sll'ber ~t !!.=. (ti18). Ale, ill bepa'-aa an lMHa.ed
.. ati. of alYoolJ.l .... aooc.panled _ a ... p rl •• 1a
rK ~yel (Shonk.!!. al., 19661 Oorban, lQ18J bahl-al
n.!l:... 10'18). Bo ....... a,dow (l'VO) did DO' tlGd .,
I" .... kabl. ohanp 1D fa: .. 'lYl1;, 10 ~"_OeJlOua ... ,
llv... l' baa b •• n obaene4 tbat 1rl t .... a bays.a. ..
h1ah l ... ~ . td Pit tlaa' thia total. lncr..... I.e PK 1 ... Sill.,
oontrlbuted _ • sharp rl •• In tbe PK "p. II otlyl_
e .. lDboua • .!! 1'1.,. 19'12) ..
ft, t.a, t1nd ..... a1 111..... ta &11 *- k4q
•• ,... of 81,0017.'. at ... par'lal bepateot;ollf •• 1. alao
22'7
ob .... ed 1ft h.p.to..... A ••• '10 1801'" •••• 1ft
...... .,.. •• 111 rapl41, powlng lMpato ... aM •
rac1u.otlOD lD Pl-.eo ... 1.,8-cSlphoapha ••• , G170eraltlehJ4 ..
I-Fboaph.t. 4._('11"0' ..... an4 ibo.aphosluoon' •••• _
Sen_aU, obaeP¥e4 1D tbe.. 'WIO.. (aboD.!1.au.. 19&6).
Ttl. tn_depen4eDO. ot th... ..,'" _ .. oo .. n a\lpp1r
ot aDP and A~' aboul4 .04ul.'. \belP ca'.bolla aotlYltl •• th .. ., al tw1Da tIM PI[ _"-.1".
Tb. 1 .. ' au,_ of 811001, Uo patbwq 1... L1lB
&leo J:-_a1nH hlP_ Sa PIP'tal17 hepateo'-i." _Saal •
• , all , ... atuclJ lauryal .... oep' a' 8 Jut wba •
4_N •••••• oba ... .s (Table te). awl.,. pat' ... ot
tUB ..... 4..aatttated 4urlaa apontmeoul "eYelo,..' 01
.. lip-OJ and baa beeo to\lD.Cl that tMa. ob ....
preo.e4 Il\101\ ... 11er thaD the sponteneo".4eYtt1opaeD,
of aallsnano7 !!!. 9,1 tro (O\udnaka.!l.!l.t.t 1"8) • AD
1DcJt.... In um ao'1.1~, ••• &1_ 00'10ecl In Ibrl10h •• olt •• oells (8rlDk11ortb an4 ... , .... 1918) aDd 1D
IUtaal.'10 ' .. ora (lSiel'll.' IIDd ouSaar"" li1a).
U •• bay. an 0 •• ral1 vl0. ora th... -.,. •• 4taou ••• d abOYI, •• tind ..... 81 mr .... 1D .. a. ot
228
.17001,.1. 1ft par'1al1, bttpat.o'-1a_ oel1.. t.b.
hlpttr 81,001,tl0 aotlYl'7 cum ••• u, b. oorrtt1ate4
with d .... aaed 117008- oODt." ob •• " .. at .. " .. 11a1
~p.t"to., (Sluk.!l!l!.. lGe8, x. •• , al •• lH8, live).
X, app.ar. a., eM •• anoed avol>10 "".01,'1. &0".1" 1, D.S.~ ... tund_.'al D~ • D •••• ..., ppop ... of
ullpanOJ. aa __ 81UGo,. 1. r.qull'e4 a. a ba.s.c.
eDeJ-g .ouro. 1l'1 all tbe 4tY141q oel1.. A dl.tcSlDa cell 1. ba.loal17 1ft neeil or high .. oo __ vatt-. 01
aacrOllOl .. nal. •• 810b are thousht to b. prcw14e4 bJ tb.e
aalnteDeo. ot e1e.ate4 1 ... 1. of 811001,t1. lD' ...
Mdlat •• U Pl"eOVllOl'a ot aaora.oleoul.. (Roo. &D4 140 ••
le~). l' 1. reporhd th&.O • larse .$ore of aao..,. 1I01HUlU'" pp .. urllOra 1. 'bull' up c" ... loa ttl • ..,.1'01
pba •• ot \he oell 0Jole ••• prelu4. to .. oroao1 •• ul. ••
'7ntbe... (a •• ob.!l.l1:.. 18'18). A. reported lD ,be
~.'eD' la: •• ,Ulattoll. a bJ.&b. pat. ot &l7~lJ.l. a4
4ecre.ae4 aotlvltl •• ot Oluco ••• e.pko.pba .... aDS
!Prtucto ..... pho.h.'... lD deyelopbg rat 11.. _ •••
• hip capaol.tJ or 817001.01, .1. an4 au'b'~Il'
&170017-1. and. tbaC sJ.uoo •• d ... &4 •• 1011 rather' thaD
-.rath •• i • 1. .. .a~or •• t.bolio patbwaJ to dlv141Ql aa4
4 .. eloplll1 .. a' 11 .... (\~.bep and Can'eo. 1i&'1 •• bJ
wallaoe aD4 .... hol_. 196'1).
22D
QluOo.",-6-pboapbatle 4eb1drcgQl1aa. alto ab ••
an eDhanead ltilvu or ita aotlvlt, 11\ p8l"Uall, b-.patec-
toalaed anJ.q}. (Table G6) wben oOIlPIdJ.4 with abaa-
operated cOQ-WOla. 1'he •• t lndlnp .....uPPOl'ted ..,
the oba .... tlona of .lODe. (1966) who ob..... • ltlpr
11.er (J6.P-na aotl"fltJ After papt14\! ablatloll of l1v.
in ,..at. An loore ... .a .otl.1ty ot asp .... DB II1cht be
rolated to an increaaed ava1labl11tJ of Sluca .... . pbo~pha,. &ad tltl. 1a.er ... 4t4 produottcm ot sllIOo ..... .
pbosphat. ou b. larS_1, account" tor bJ ~. p1" ..... .
or t.be aclaptl ... OllQ" glucokina... ADot~ tactor whiob coul.Cl oon~1,*t. ~ ttl. in.re ... cocoe=.atlO1la or pucos_-pboapbate 1. the 1'.latl't'e1, 10. -.ot191_
of gluoo • ..e-pho.pba.... in I' •• .oera __ 11... (".n. an6 C..,teo. 196'11 wallac. and 1I .. ~. lOS?). .&1.0
In Mpatolaa.. tID 10 ..... _ a.'1n tJ of OSr-DH baa --
reporte4 bJ eo .." bYe.tiptop. (Iod •• eud. ltel4. lV.a. Weber .!!. ~'t. liS6, IlalAtUl u4 Bro_. 191f, Iot' • .!l.!lu 19S8). !'heee _tllOJ'S .,lao ... ported a • .., 1 •• 001l0U·
"a'lOft or BADP lD 11., .. t-.orl and the ... ka4 .... lol1Na' 1n bepato .. GlP-DB aotlylt, Is lntr1pl. 11l '1'1 •• o~
the YerJ low ecmooAtratlon of tbe flUttl_tl.... Allo. in
'.\a1 I!'a' (Burch !l al.,. 191&) an4 au1n .. plC 11 .....
(I. •• an4 walk_. 100.) an lacweaae4 _t1v1" of 08'-l1BJ
230
••• o'b.et~*,. It 1. lera .. all, ooa.yecl th., 4\&rs.. .
preo4UlOflrOua phaaoa, llv .. 1. belog r1ch !.Xl lattl ao14
content (stanUa .. 1969) _6 Il hlsbor aotlvit, ot 06P.OO
baa a direot relation with this u 1b 1. the ... la aoupoe
at KAPPB required tor rattr aold a,rnsheala.
In tu.ora, the en.,... ot BlIP IhuDt require
particUlar attention due to Itrategio polittoa in tbe
k.,. branoh pOint ot Sluco .... e-pb.oapb.'. par'l'loulaa be' ... 817001, ••• aDd tbe BlIP .buD'_ the ..... of
81P ttl., •• t n ..... ut 1DeP.... duvluS o.u Pl"oll.
t etta.1OD aiDee 1.. tVl"lllab.. pento ... tor DUol.10 aoi.
8Jntbeala, HAllPB tor reduotion a04 in' ..... 1 ..... toP U"O .. u.o rl,.. .7ath •• la. Ir ••• , t1tltu'osa 1ft ¥tea--·
. I'a'ifta 119'- are 1a 11.,. .1t1l the b •• to Nqulr __ ' •
•• ,.bl1abe4 tor proolU.atlng cella. th. t.no.reaa_ aoti.ltl or eDa,... a8J t_t.'1 ... 1J be atv1but" '0 tb. .apP ••• IOD of .11eDt .enetic loel OP to tn. ebana ••
of •• ne oopt.. .llclted " prolltcraClon 1a4uoed tpanafOl"_'lon. It 1. alao 11kel, ~&t •• leotloa 1.
aD ~'ant faetop In tb. ebol0. or • SaD. _apre.aloa p.tt. ... n oob ... nt with oell ppolUera'lca.
the p~o~.nt .arl •• ot eaperl~t r ••• alstbat 'ba
.ax"- 06 '.00 ino ...... 1. Ob .... 84 at 86 br .beD tIM
231
fira' peak ot IIltotlo lDdu 1 •• ...,.ct-e4..u ~. iD
the fable M, •• ean el."lJ yl.uall .. that. .... a.,t.l_ ... ,. lnol' ••• lna ., 1& hi- at,,, aure., ODlJ aD' ..... r_lna hlper tbroushout the ob ...... 'I011 period. . A'
il br, It 1. DOt .1pUloan'l, AUt_en' I'roa tba, or .ba-oort'l"Ol.. It the coaparl.oD Ie .... UlOft& U.
.~J lDtel'Ya1., we ... that the. 1 •• Itllarp .,1 •• 10
8O'lyltJ 'Ul U' bit ahowla.g ..... 1awI need or .ADPH. ...
rlbo ... 8-pboapbate tor nucl810 aold tr0th •• la wban
0_11. are in pre-r-V1l0.tlv. pha.. and pr.apar1na
tbeII •• l",e. 1"01" o ell. 41 ... 1.100. then the aot1'1'1" arad\la111
4eor •• 88fJ indloatlng • deol"easod l"'Gqu1rament of
PtteUl"att.s of .acJ!'OJIloleculA1' ., la'wintl ..... al ••
IIall0 .SJ" (flabla 61) alao .0 .. an a),lIOa'
.1IIUar patOel'l'l or .otlylty 1P partlall, h.pahe' •• " ardmal •• e Oel-tri 4o.a. 'lb. ODlJ dltt.-fIllO. la tha,
tbe &0'1 ... 1#07 '01 n r.a.obe. '" .Lt. peak at .... at ... aura", ana Wt.n .... t. 4.oJ. J.aiaa lnl' s., .Ull. r.uu
41p1t1can'l., biglwr thSn that of ab __ ooDtrol.. J1allo
.DC'll- alao 1nd1l'ecUl7 belp. 1D 11p08_0• 18 .... ,
p.redue.oa ftADfll.. All lncNaa. 1n MS alona with 061-1»1
.s.gbt 1n41oat. that the J,rOMtrnt mot!,,;!." of GI,-Dli 0IllJ
t. DO' able to l!I.tee' 'bba Hctulr_ent ot o.u. AD
232
bor •• eel .. tl'1'1',. or tIS b •• atao be. POllIa to b.
1»" ..... & duPleg tbe POat.tal 4 •• e1opull' ot .... 11'1'''' (Oea. 19?8). 10 otb .. ".POJl' aD tbl. 1a " .. .....
r.tlog 11 ... 1 •••• nabl.. 80 ....... 1D hepato ... ull •
• ..,.. .... .s.ttser ab_.t or aub.tan'1a117 4 ..... ..
(SboDk .!l.!1u 198&, JIoIoI"l •• 1878, y.,l.OP .d..!lu 18' ••
Qp~__ aDd. Swka. 1;';). 'ftd.. 4........ ... . ... AtlallJ
l"epor'" to be dq to 1.0.,1110 ahltt 1D cU.tt ... , oeU
1...... ~ the b •• ' of III kDowle4&. 0I'llJ Olll! ".par' 1. there whloh lattloat.. 8ft .... eel 1 ••• 1 of Mllo .. ,..
1I'l tutp.toaa B\ (llorr1., lU'IS).
'1'01111 DJI.l oODt.nt alao abowl aD wr...... 1 ... eJ,
III par'lal1J hep.'''toalu4 11... (f.ble .'). All
e1 ••• tla 1D _.1.10 &014 oontent at,.. .eUal hep ..
,.eo., ba. el .. been r.port. __ ..... al 1a9 •• 'l& ..... J! vl'19 (~ S. al •• 1181, tboap,OIl !l al •• liU.
81aoheJ't .!1!l:,.. tt •• , Pulml. 19t'11. Sbort.t! alII 187&)
aDd !a .&""t;t, (8Mb''''' lID" •• 1888, 0004 .. ..
80th.,.... 18"18). A hUDdJ'..t PeP 0.' lDozt .... la DIA
"'tID' at,,, p .. 'lal upat •• to.. baa b ....... ,.t... Sa
ra' '" Jlrod! aa4 hi. ."08lat.. (18Ge). In &he ~ •• _, ... " •• tl •• ,l_, an lDor •••• of alaUu •• aa1t\l4. 1. _'10.4 at 2' _ -',_ auq.,. ODe po •• 1blll.., to •
.u lDor ••• ect Gont .. , of DIIA att. aur • .., ..., "'. due
233
to tbe eDtrJ ot 1DOr ... .s mala.!" or oell. lDto proll.
f •• 'loa ao""It7 81ld •• t1llul.'." path • ., of .,1I141De
_'111""011 and • auppr ••• 1OD or tb. depr ••• -' path • ., or 'lV1I141ft8 oa,aboll... fb1. lnt48'pre'.tton 1,' lD
I.&I'..-nt wltb th. _'wU •• of Labo • .!1 al, (1.9) WDo
atuc11e4 1: •• eDSJ_' or __ ldlDe •• ,.bollaa. !be. lm:re_
1ft 'o'al DS. oon'_' at, .. partial bepateo'o., 1. sa coatlnltJ with the tlft41aaa of atoker and eroo.. (10.7).
C8Ilella1d.. .!!.!!:. (1D&9). Heoht ud ,.,t,.. ( 198fl ) • a..Y\rJ...
Aloand. .. and !oJ'- (1S'lI). Pl'e.10l1. work 1ft ,bt. labor.tor, al.o 4..,"'.tr ...... ahano.4 Up" of aa.~411ltl at,,, put,tal bepateotoaJ (Db!'. _p811-..
.".Jc). ""01 a1l4 Lal.. (1910) .. epoJ'ted an Inor ••• eel OIl
eem'.' of the ........ maallua att .. partial &bla'loo
of 11~. Llke OUl' pr ••• t tlll41aaa (!'abl •• 7), tbef altlO _'ioed • rtaUkUl. d.e ..... 1D. ttu. nlA p ..
11\101-. att. 1M bit in .a' 11.... !he ..... k ...
__ .,e4 tha, the oel1. doubl,", "11' DI. u4 ftlA SA
the .al1 plIDul. UlCl auperaa,.t fl'ao,l_ beto ••
41ri.41q. Ae the oeU.a dl'l14e4, the _ele10 &014 .....
41.trl1»u.e4 __ the d"'e .el1. &04 th ••• D •• otall •
.... -.ppreol.ablJ 4.tlo1ent 1ft _elel0 &014 (U.\). A
.1pUtout lIlor •••• lD the 1 ••• 1 ot OIA ., 6 Nt roll0 •••
'" It. a"'talaS.Da • peak 1 .... 1 at 2. bI' 1. u 1II410a'108
234
\hat .a' or the paPaohJ_lceU. bash the proce ••
ot dlYlaloft at the .... tt.e. !bl. woUld ~ •• , ~
i·'; poaalbUlt7 of • m.oz.al •• ohmi .. tar its. lat'la'loa
ot II1to,l.. Buobel-.u..!l.:. (1850) ob'a1nad .. 14.0. t.
a blo04-'boPae _ohani. tor the regula'lcm of 11 ...
o~l II1to ... wba t~ touMua lDoIt •• ae4 rat. or alto.l, III the "IIODOp ....... -poablotto partn .. of •
,
, .. _a11, h.poteo~Jd .. d rat.
Aa .. 'lonaCl ... 11_ 1Il the 1"8vl •• or 11 "".t\ire,
11"01.10 ac14, an4 Pl"Ot.lIl. pla, aD *lUal.lJ lapol't._
1'01e III res_ •• 'lba 11y .. " Table 'a· AD4 '18aho •• 'al
aa4 101u'b10 pJ"o,.s.n conten' r •• peotlve1J In •• Ie •• 'lns 11... Solultle ~o'.1D OOl1,.t t. toUD4 to be h1&ba'
UWl ~ toW prot.ln. one po •• lbU!" 1. tha,
b •• u •• of tb •• apld dl.lnt.aratlon ot the .eJIbro.e,-ot .-lopla"" .... tlo\11 •• and 41.perat.cm of rlbo ....
tia'oUPOUt the .,_,1 ... (S-uot m4 B_.c1."l. 1980).
the 11poprot.lD .e_ant. of tbe cU..tn'.pate ........
~u. oould r...sa s.n th. tPpel'Dat&llt d\lJ'1D& ae41-"D'a'lOll, tbua ool1trlbutlDg to the aoluble pro,.sa ooo'en' or t'be 'l.,u.. All o".,.all s.ae..... Sa paaotdA oont., at,.. aupa.., 1A the pr •• ant •• UdJ 1. SA liD.
wlUl the ob .... atlcma or lI.belt (11;61) -.4 SoorDUe ao4
Io'Dol (1978). Shwt gel hi. co.rae... (IV'S) ... pOI"'_
235
aD iDor •••• 10 the rat. of llv .. prot.1n IJDth •• l. SA
the pr ... pllo.tl •• perlocl att .. .aura..,. Alao. all
loer.... 1n hepatl0 rlbo.o.. toraatloo attaraurl.., •• ported '" Ohaudbu-l .!1.!1:=. (1M.) om be • I' ••• oa
t.. lnor •••• ct prot.sa ')'I1th •• la at,,,, pap,tal.
bepa, .. to.,.. SOOl'uJr (1i'1.) alao tollD4 &I'l laore •••
In tbe ppopOl"tloD of rlbo.... In polJl"lbo ....
4uJt Ins •• ,enel'at1Ofl, whf.oh r_.1,.et lG 1001' __ 4
prot.ln .",tb •• S... Gl .... (10'13) •• port.d an lneNA ••
in nuclear an4 rlboaoUl RIA 1rl partlallJ ablat.,
11.... Seornlk and Botbol (1;78) t.aJtther reported
lat .. on that dur1ng the tlr.' tMrtJ ala MV
ot 11 •• 1" r.aeneratlon, the ......... !J.t. ot prot.iD
d'paactatioD \bat abow.e4 40n ct.tera1De4 the -.aluo.
bet •• en prot.1n .,nth •• la aza4 _, proteiD GOnt.Dt.
U thl. la tbe et.teot affalr 1D thit pr.,.llt .tv._ •• oan un4e,...t_d w_ proteill oont.t haa ccme hl.
in IIOU.. l1yeJ' at'er aur,..,. Ho ••• ", d.er.... la
total Protel. GOntent at '72 br (Tabl. '1&) 1. aurpplalq
and the 01117 aupportlDf! ob ..... '10' '0 the be., ot ., _owle4l&e. I, of Om-d eel M. ..ao.late. (1 M8)
who ob'.1'9.4 that rat. of .ppe __ o. or ne .. pa-ot.1ft
236
~o • .s: dowa. at ... tlJta' two 481. or ......... '1_.
"p • .!l.!la. (1968) no'10. a 4 ....... lD *. ~'al .o1ub1. pro'.SA oort-e.pon41ng to ,he ,'- of b1ahe.' 111'0'10 ao,",IYltJ •• ob..,.ed '" auel1aJd. •. and hi.
ooworker. (1(U;t1). fbi. ob .... l.' •• 'be po •• lbll1"
that IOU IptteUl0 prot.m or & n-aotloD or It .., be
• rqulatorJ tao1soP la proteSn qAth •• la whlob )rOO •••
t. Itequlat'e toJ' oe11ul..,. bJP"'Wo~.
Bt,.o' ot I*BA OIl ... S.OUI .!
(""ii pe~ oent) ~ BII ('""'II Pel' OeDt). thoUJ,b bo~
tne en.,... are lDhlblt*" 1, app • .-. fib-' th._ ....
80 •• lao.,ale eltt attw carolnogen C",e.tllent.
Oluookla... alec thowed a 4.01" ••• 14 &O'lYltJ ~
oOliparecJ to Uftt:r •• ta4 pU'tlall, h.pa'.o~.ed • .sJld.
and It, la •• l tall. auob balo- __ t ot the Ib .. -opera'*, Antal. (fable ~1 m" 'lave 21). Otb .. .., ... o~
gl,ool,.1. ".1 (Table 87 and Fleur. 2&). Pit (Table Q
.. Piaur. 28) aa4 LDR (fable '" and 'laut'". a&) ....
alao lr.tb1111'-'. ,., au1lNa dNr ..... a. ob •• y." 1D
UK ao,t'dt)'. tboup P'K aDd PJt are ~. ke, .n., .... tir.t regulator)' .lte of &11001181 ...... t;o be
n.xoktn ... oa'&1,04 reaotlon. A 4 .. ,....e tn all
th... ....,... 1. an 1Il41oatloa of ....... e4 raC. of
81'001,.1. III the res-..... 'lna 11ver aub •• quent to It.
upolRl1l'. to t~ e ... ol.8 ••
0eneJ"a11, In hap.to... (.U7iber ch •• loall,.
ln4uoed OJ" .pontaneou8). an anhanced 1".'. of sl,ool, el.
1. observed (w.ber. 1971. Glook and JIOLeua. 19&8, 19M,
Monakboy.!l al •• 19'5).. lD 11 ... ~r. 1Jl4ucH bJ (U ... th,lbJ'dr •• ln. (MonaJcboy.!! ,81 •• 197&) DAB (·MaDJe.w ..
e' 4., 1966. aoJ..ban. 1996) wad warloua other obaaioala --(Sate> .!l Jl.,u 19'161 Yon .. l !!.!!".. 19'71) luOl'."ect
aotlyltl •• of all ~. kar .n.,. •• ot sl1oo17.18 polD~
238
ou' _ an .duma" rat. or &11001,.1.. eo ..... , liIldo
and bi. o01lOrk ... (1872) c11d aot :t1D4 aftJ Obana- 1D PIt &0 •• 1_.
A deoNU. la LOB aotl .. 't, In the pro ... '
lD.v •• UaatlOD att.,. aeoboa_ .... ,MDt 1. well
wPpor'" 'b7 the ob ..... tlOft ot Grubb. !!. ~. (19"&)
&0 tound a dec,..... lIS .L.JJ4 att.. 0011014&1 a ..... IOll
ot PAR in ou,l.. 8140w (18'10). alec r.por'. ataU .. ...... tlol\ll.
ft. cl ....... 10 aU the.. eDa,.".' le.el. GOUld
'be baoaua. ot the ... 1 •••• of oellular m.,. ... iD_ cell
»1.- due '0 mor ..... ' .... bUlt' or " .... an .. .. art ino .. ueel ao'1"1,, of th ••• en.,... 1. ob ..... 4 ill ._. (WleokowaJd.. 1V'S). our r.aul' •• bo ........ do
DOt 10 ..u .IUi .ht) •• otBelJa.y& (1118) .bo 0» ......
tm .... ad 117001,.1. a.a4 a .-1 •• III IDrJ ao'1ylt, SIs
INIIO •• la4uo_ '-' .. tbel- 'AB-a."~lobo1aatbr_ ••
A 4.01' .... 1D all th ••• en.,. ••• , 'bl. 40 ••
1 •• 81 of the euolms.u w1l1ob 1. quit. blab I, probabll
Wlc"tS". ot • toxio eft..". elob uaua117 0_., ••• n ~, • low.r do.. ~o4uotng ......... br.ne "'ase.
239
Ad......... 111 OIP-DB 80'S. 91 tJ ('able la ...
Pip. 3'1) in DJ1B4 expo.ed rea.era'lna 11... 1. al ••
\1Dl.1k. full _own Mpatow.. where an 81 • .,.t*, 18.,el. ot
till, en.,.. 1 •• ePGl'M.. 8h'k.!!.!l:. (19'1') ha"
•• paned aD lDor.... la oar-ns •• t1 '1'1'1 Sa aloe
adJdnl.MP'" with Dmt. AO.tJl •• laofluOJ'''. alao
'.«\'&Oed aD Snor •••• lD 08P-J)S &o'I'f1"lD .a' 11 .....
(P01rler ,!! . .!!.:,., U169). A 4eore... 1n .&lie • ., ..
in ~he p~ •• ent study at'«r DIDA tr •• t~$nt (~&bl. &1 an4 PiFe 41) how.Yer, 1. oompa"able to ,_ 4eor ....
1n the &otly!t, obaetty_ In ,..t" tett OheahU oarobS-(Ta,lor- .!1 61 •• 197~). 1.n l'aplt1lJ ...... owlq hep.to_
(Shonk at al.. 1985) and 1ft. tbe llv ... or tuaor Marlna --rat. (az.aJow" and Surka, 19?9). With tb ••• .uable
liter.,ure. It 1. dlttloUl t to con.l.t. 'be otwnae. 1n .. 110 .a.1M aotl'1'1t1 atter De. tit •• , .. , .. 4eYalopa-.' ot neopl ... la. Morrl. (1''12) •• po"- .. ,
4eoH ••• 1ft IIallc &0.1_ actl'l'lt} 1ft ... lou 'u.oJt oell
liMa ....... entlal17 due to lao.,.1o .bUt 1 ...
ena.,. .01.0\11 •• _verna" br oofttll'11a'lODal van ... tor .. tlon In tbe pn. r •• ponalbl.. tem 1'. "A~al ••
A 4eore .. e 1l'l total nl. oontent; ill tbe pr ••• '
atl1_ (Table a, aD4 PlsUl'. 'IS) .". 1)111. &4.lI.al.w •• loa
In _'Mel. -ltb rogen.at1D8 11 •• oonfir .. OUl' pl"e.s.o'U
240
..... atton. (Disi' .. Rao. 1880). A 4.01' .... In
_'Ill DRA oonhDt and 1t. blo.,atbe.l. baa al., be. Gb ... ". in res._a,trag "a' 11... atter DIBA "' .. __
'Marquard' -114 RaUl,., 19'181 "'que-dt.!.! al •• l'VI)
re.\<lag 18 aD 1Db1bl'lOft ot lnc" .... 111 0.11 IlllUe
laduo*' .., p .. ,s.al bepat •• ,OIII. DIA oon,.t .a. J-ec1uo"
to about 38 pep 0-" or untr •• ,. "&1"1-'17 ~pa,"to-
111." oolltl"ol a' '18 br.
cnu- .... ult. e. 1ft Good e .... unt with that ot AltI-e4 Ul4 D:'paolo (1988) Who observed III) IDecU .• t. auppr ••• 1oD of DBA blolrnthee1. 10 h ... ,~ .-br70 "
DMSA. !b.,. DOtloec1 that treatment of cella witb DOA
on.eel a 4.1.,. in tbe tlae norma1lJ required. tosa r.acb.1ns th. mulawa rate or DlfA aJDtheala .. ..u ... a .uppre •• lcm. of altotlo &eatlv1 tJ' -'188e.'Ih1 til., • po •• ibl. blooh • .s.oal 1 •• 10D ocoured at .oae pola.' Sa the path • .,. \0 the oo.apl.tlOD of DIIA .,Dth • ..u. 4fbe
".ault. are In contora1t, wltD tho •• ot Jllbn a1l4 ft'041
(lM&) and JerlJko •• Jd. .!!.!!:. (lV98). A .1JaUar
4..,...... 1D DiA content, Db .,nth •• 18 _4 tail.. of
Jd.totl0 at1llulua or partial bepat.o1oliJ ••• 1D4uo" '-1 oth&1.' bep.' iC"4 . _ oU'olrlosena 11ke Aoef;Jl • .s_fluo.e.
(Jaokaoa and lrwlrlg, lG"3). Dla.'h1lDltroa..s.n.
241
(ste .... t aDd. ...... 19'1). aaod)'. CSaruarJ". lG6&' • ... t.llvoqu1Dollno (&rold.!!.!!,:., 1970)" HJQPox,._ and I.hroaptopurln. (tM!!.!!.:.. laVO).
th. eel •• ,l •• -.. trmaleat ... teo'. of DOA Oil
9 .. 10"8 .l1&Jae_ and DB _1 .. ,,108 lIlala. 'he .ttee'.
ot 1"a41a'lon (Vant.nok... 1980, tAba., .. 4 Oka.a, 1~1&, b,
0 .... 18'10) with the .seep'lOD of JUl10 _.,... loth the
as-'a 4.,.&, ••• m ... tl_ 111 l'a'a. The 1ft'''''''. of DMBA .1th DBA .,nth.ala ba. bMn. d_OIlatraW 1n •
wi4. " .. letJ of 41.td1n& tl ....... !9 ..... _two-.- (Alfr •• ,
lOSa, AJ.f'I'ed .,.4 Dlp.aolo, 19se) aa4 !9 1190 ,.ca .. ,_ aM Quaatlllr, 19&2, J.a. !.! ~., 19&1. Sbl.kln ;!lal.,
1,",'1, U_tau a04 Huatna. 1868 -.1». fbUl., • .!1 al., li10). III ... 11er iDv •• tlsatlcma on l,".OIIal •• ,..
n.oa,rlbor1lo1.... 1 alM auppcwta • 4....... ill DI.l cont_t at,,,, DeA .... ta_, .. _I..ala tr •• ted '111~
IlIBA ahow.c1 _ inoreaaeel .ot191" ot MAe. (Olal:', 1~'9).
!b.erer01"e. a deer ... ed DRA oon'.' 1, DOt 0111, beeau .. ot DEA -lDd\ae" '\lppp.a.e4 pathw., of DJI& blo.,nUleala (70111,..,* !!. al.. 18'10) _ut, a1ao beoa".. of at111Ulatd
oa'.boll.. of DlA.
PH •• 10 eon'ent al., abo... • 4...... 1D .. SA
.... M4 1" ...... '1118 11 ... (4fable ,a _ 'It, Plaure 6e
242
ad U). A partial rHOY.., ••• 0 .... .,. at, .. 38 U
Wbloh le4 to tan inor.... at '12 br C V\ a8 pflt' 0.'). A
.eo,..a.. 1ft pro,.1ft aJDtb. •• l. ha. alP.a4JIMeJl report_ ill DM8A -v •• ,_ petlallJ up.teatOlll ... 11 ... eY_
art... I; 4a7. of Ir •• tunt (Dixit e4 BIIO. 1WO). A.
... S .. l lablbl'loa or total aDd aolubl. prot.ln oonteD'
... _tlced ., Ie and. 31 ... r •• peotty.t.J. .l taU Sa
proteiD oODten' in o .. o1Dos.n-.... '.c1 ....... t1 ...
11 ... ba. alto .... reported b7 .taohi (19'13) ••
S'eart aDd ..... (19'11). tt. 4_" ••• lD labell ••
aalDo ac14 ltaeorpor.'lon in pZlO'e1D at"" OtIPolDO&_ a4alnlatrattOD. _e aoOOllPazde4 -., an 1nblbltlcm or RIA
.,nth •• l. alae (Prio. Ul4 Laird, 1860, st ...... , u4
-as •• , 19'11). 'lb. 4.0 ••••• ill prot.lD OODt.t a' 8 bJ'
at,,, 0.&01.",.,100 of tbe 0&1'01110&- •• Q1d M he ......
ot the 4apen4enoe of lbbibltloll ot pl'ot.la .,.at.la.a1. on the _'aboll. ot th. a .. olDos. to a ••• '1 ••
.. _latiq m, .... U.a'.. the r ... of produo'ion of
_01\ _ lD'tIl'Md1ah be1bs 4.01'.". 111 Ute Ph,.in
4.ple'-4 ant.al. (4eel' .... 1D pro'eiD oont_' broup' by
about lthe oar.inogen 1t."") au4 tbeP.t01". abowiDa • par,tal rHO • .., ot prohs.a oont_, ., 92 bJt. CODHque'
10 •• la cgl PI'O,.lll a •• S.'lY1t, .., haY. 01> ......... lr oal'olllOS __ ladUee4 cbaDe.. in RD .,n .... 1.. A ""NU.
243
In R.A. ooateM •• port.t ear11er (DSal' a4 Reo, 1980)
1ft r.seaeratln& l1ycr att.r DIBA adatnl.tra'lon IUpport.
the pr •• en' tlndlq.
n.ar ••• eeS .atty!" •• ot a1JcolJu'o en.,... Ja
.u-olool __ tr •• tect _Saal, aro oonal.'.n, with ,be
deGre.,'" DI A OODttmt and DBA bloaJftth •• l. 1D tb.
tre.ted aal.ala •• reporte4 1ft tbe pr •• ent Sa.e.'Is.tuG and ... lier. Slnc. DiBA bP1na •• bout aD iDblbl'lOD ot
Idtot10 au.lN1ua bJ partial bepateotolll. ceU. 40 DO' ne_ IIUOb at e.-r1J ct .. 1.84 fltoa 8170011'10 pau.waJ
ad BlIP _.t _4 theretor. auto •• tlo.,.lJ the .n.,..
HtS..l,S. •• ar. decr ••• ed. .., •• wante4 - ......
whether the bloobeldoal ebaracterl.t1oa of a ohea1o.17-llldUee4 bepato_ ... alao leen at 't. lal'latlon ph •••
OP DO.' It 1. 01 ... tJ"oa tbe ~ •• _. lD •• nla.tlOD ,bat •• tar .. the.. par._'... are ooacene4 lD DMBA tr •• ted
_iIIala, DJIBA lDitlall, br1D&' abo,," • cleeHU. In
...-lou. en.,_ ao'1'11tl .. , ID4 DR. a. pJ"o'.la eOD"" wb~ •• ' • b1&b level. of t~.. bloo~oa1 con.tlt.eAt. ... au ... alll ob ... .,.s 10 _opl •• Uc 11 ... o.n •• Con •• q,uenUJ l4._Uloa'loD and lDterp".'.'lOll ot tbe earl, eft.o'. ot DMBA ill "e.eIler.tlns 11Yer ,.bleb • .,
or .., DO' ". neo ••• .., tor th. PJ'oduo\lOD ot 11 •••
244
tu.r.) baa _.eo ...... ctlttlCN1t bJ lnt.ter.noe trOll
•• nlt •• '.tiona ot the acu,.l, toxlo .tt.at. ot 'be obellioll1 lB •• ,eDe .. atlna 11 ... oel1 ••
,Intlunce of .,0 OD DMM lnduotld bl00b.~a1
cbS-' In pu._a!_ .,u! ,& • ."
JIPO. .bell ,iYeD 1ntJeaperltoneal.17 to partlaU7
hepa'ectoJdae4 ale •• brlna. about aD el.y.tlOD la ..
total actlYStJ ot s.xoklna •• (Tabl. 1t and Plpr. 8).
Th. aotlyltl •• of ma and DUI alao cbana- after .PO
a4ll1D.lavatloD and It I, cl • ..,. tJ"oa the Tabl •• aD an4
21 an4 Pip.. d and l' that tb.,.. ocoure4 ., J..oqal •
• hitt 1D thl. &roup ot .xp.rJ.&eI1,.l anSaal.. HI
".Sl.t ... am horea •• at all the 1at .. "a1 • .ao4tpt a' 2. br ~D • d.or.... or .~u, 21 peP O«Dt wa. DOt10.4 where.. HltlI Ibft. CD lno,..... ., thi. In, ... a1. ~
total 1rl0l" •••• 1ft UK actlnt, app.ar. to b ••• 1Dl,
beoau •• or _ lnor'"'' '1btbe.la of It. 1'0.,.' UI.
Blab ... Ol\lCoklau. (Table &2 tmd Pl&"" .21) 1 •
• 1snltloantll enhanoe4 r.aohlna to 1t. aax1ll\a aotly1', at 2. hr. Othes- k.,. en...,- or alJoo1J.l.-pPK (Tabl. 38
tm4 Plgur. 2&) I.. GOt .S.p1tl0aftt17 al--- an4
r ... iDe4 in DONal .. -na .... pt at '18 - .bla ... all
245
cleoNa.. of about 13 pw cent .... aotlol14. ".\1 .... " kiu.. 1. a1_ 4eor ... ed (t.bl. •• &ad Flsur. £t) bu'
tbl. 4.01'.... 1 •• "" 1... 1ft DO " •• '114 p.tlaUr IutpataotDlIlI-' a1laal.. Bo ...... LOB eo .... • SpUleentl, _haooe4 80tl.1_ at. all the .tUdJ lDtvvala. Aft incre ••• 1. ob ....... _ t111 18 br 8t14
tb.n It 00 ••• down 'but at111 r_a1DI hlsher thaft
1ib., of partlall, bep.~ .. toa1l_ oontrol ('fable 60
cd Figur. U). 10 81p1tloan' ohana- .a. brouah'
about 1n oar-DB .o'1.1t7 when ooapare4 to lmtl" •• W
pur-UallJ hepabeotoalM4 controls (Table 51 ...
FlgUr. 37) Jet the aot1v1t1 •• at 41ft., .. , lIlt .. ".l.
.... 1... thaD thO •• ob..... 1ft _tr.ated ooatl'ol ••
Italic en., .. aotlvit, ialtlall, decreased aDd ,beD
.a" 00_1.'ot1y blab-- than that ot \Ul ••• t*, ubal.
(fabl. 68 and Figure 411. !he pr •• ent irlv •• ts.aa'iOD .U.PP01 .. t. ~ o1>.erYatloo. of Bal..auo d al, (H~'2) ••
notloed a .1plfloant enhmo .. ent 1rl sl1oeral.4ebJ4e-1-
phoapbate Cl,-drol8D&... LDB and ATP with a .1iP'
41a1DUtlO1l of QlP-DB. A. oba .... e4 in ~ pre .. '
In .... Upclon, the, &l.o 414 not flnc1 aDJ .-._.able
ohllDS. lD. ,1.. With the .vaUable 4ata, ltooul.4 btl
oODOlu4e4 tbat JlPQ enhanc •• 9arloua efta1_'10 pr-ae •••••
SA a--ral. Row .... )& 4.01" •••• t.D PIt 40 •• aot t •• tUJ
248
lD ta.o,. at an 80081 ... ,.4 11Jool~.1.. wbll'e.a an
el •• a'ed LDH and Q 80tl.1tl •• are alp of incH ....
. a.all.bUtt, ot BAlm whlob 0_ b. uaed tor o.Uul.-
.... ., .xptmd1ture. An er1b.anoe4 .at. ot 1170017al.
111410a'.4 111 aD iller .... lOt .0'1.1_ taw ... thAt
repOl't. ot Pqllaro (lQ56) who round tba' .IIPO eDban.,.. tbe 8110 .. 1& l'e4uolna .tt ... t. ot 1naulla. 0.- po •• l-
bUt" 1. that the \true tacl11ta'ac1 .arloua en., .. tlo ppoo..... e4 petioulaPlJ al7coaen .,.ntlwala 011 tru. 11 ... tbank. to It. PJ"lyet. deo .. boX1~atlDc ut1cm.
Total DlA oonteD' ... Wtlall,. 4_ .. _.
('able 68 ancl FipN '6) eel then t.nore .... un 26 br
(lIIli per oe"t). !be DBA 18 •• 1 qaS.D e'*"W tall"" 401111 aDd NO... 81plfloantl, lower at '12 br (V\ to ,..
Otmt). The lnoN ••• 11\ total DBA QOJltat. II&J .,.
baoauae of t •• eo., ... ( •• p •• lall, OOdfl" A) wh10h ._4 -au &rOUP 'Ear thelr •• t1yitT and th. eoU .. ,1" i.
r •• tore" .., ... &H poup ot IlPO. fha.e_ IIPO lUI pl.., all
laportat 1"01. 1ft t;ba deto.a1tJ1n& uobaD1 ...
Total pl'Otelll oODtent ('abl. " an4 's.au:r- 4V)
aho •• an bOlt.u.s 1 ••• 1 oo.pt at 1& br .ben i~ dblblttMS
• re4uoetl 1 ... 1 C V\' I. per OeDt 4.0~ •••• ). Soluble
prote1n. ocmteDt r.-1"ed al1ghtl, b1&her t111 !t bJt _4
247
thea ••• l'4tduoec:1 (fable 80 and Pipra .'). Aft
iDcr-.... In pPO_1. eonteDt .., be· bee .. _ ot at.
atlJlulatecl protein aJIltbetl. .eb1ne17 ot th. cell 0" aupp~ ••• lOD or prot.to d .... d.'loft rOQ'.. A 4.0 .....
SA eol_lo protein aQ b. attributed to tho ro411o..4
RD" .,ntheal. 1D4l.lOe4 ", JlPO .. 0.""-' lD guine.
plg. (.onna.!!.!l::., 19'12'). In .s.ce, bo .......... .
not aware ot weh atudl... WI th the a.,.11abl. da'. no oonclualoft call ba ••• that how do •• IIPO 010.a_
yarloua .Il., .. a antS pro .. s.n 10"a18 11'1 the oell ••
to atudJ the etfec' or IIPO 011 DDA-11ldUoe4
--S.. 1D •• loue •• "'" DlA and prO'alD, tlW ,_
teat oh..s.oal ..... gS..en. toae~ .. at ... par'tal
hep.'.atOlQ'. Chan ••• in y.-lou. en., .. an4 lDtlwm ..
ot DO w111 be d18auaae4 below.
!otal hezokiaa •• aotivlt, ... &108 loa1sD1tloaDtl, al tend 1a ,hi. group tba!'OlJibout the obe ..... t1011 p.rl04
e.ept at 38 hr when a ct.or.... I.. ob .... e4 C fable 1t
Mel "igUre 9). .. oan ••• that the deor.... SA tbe
tmqm8 aoti.!t, 111 tbla group or .s • ." .... aucb 1 •••
l 1.1\ 10 per oet) than that ob • .,...04 In nIQu.-tr .. t.' 1m_ala (V) 'I per oent). Thu ... notlo. that .PO ,.
OOW'lterao\1aa "POD .neo' of DIIBA OD Blt.
248
Beat .table UI1 ahow. an increa.ed actl.,., axcept
at sat br .baA the aot1.1t7 1, 4"....... Alain. proteotloD otter. bJ IlPG again.' D88l-1nduoe4 obu,. in H!l 1 ••• Dlt •• t..s (!able 20 M14ftp. 1~). 110." __ •
BII r.a1Ded t'htoreue4 at all the lnteJ'Yal. Jet ,be aetlY1tJ ... 4.0" .. .a to • low .... ten' ,baD it ...
deer •• ,_ onl,. 10 DlmA -e •• 'fMl gOllp (!able 28 u4 Plgl.are
1'1). Table 38 _4 Plaur. 91 abo- that __ ••• Ira
Oluookln ••• brougbt about by J)ltlBA in p ... tla11J hep.Moe.-
used aloe are nullified when IIro ... 81 •• n with the
oarolnosen. S1a11ar pf'otaotlol1 bJ Ill'O ... ottered to
m: (-table 38 and "lsut'e £6) and PI. (Table •• an4
Figure Bi). LOB alao 414 Dot ahow IIDJ 81p1tlomt
a1 teratlon esc ept at a hP .heD It la lnoN ••• 4 (fable 60
and Figura 3S) •
.. , thus, actio. 'hat wbtm .PO 1, Sly. with the
ou-olnoaen, lDb1"ltor,. eft.ot. ot DIIBA on .ar1oua 817oo17t10 enq-. ar •• 1that" totan, D\I1l1tle4 01' -,
le .. ' ra4uoe4. JIallo eDS1- (table 82 aDd. Pia.a 61)
al80 abo •• alal1aJt p.,'.-a. Bo ..... , aPG o0\ll4 DO'
lnt1u.no • .uob OD tbe .tte.t. ot Dl8A OD 06.-DB •• '1.1" (-table && an4 Figure '81).
249
T~a1. DIA oortterat ('f.ble es and Plpr. t&) 1ft
tbl. poup ot ant.ale al.o r_IDI 81SD1tloan'11
UDal terM uo.p' • t '2 btt _beD • 4.er.... of about l' per 0_' 18 oblS'-•• _ IE.. cozsgu. \he total. DliA
OOIl,.t 1ft thi. poup with that ot DUI ve.' ..... ala a' ft hr, ... oaD yln&11 •• that .pO ,..duc •• ,be
d.~ •• lnl .tt., of DMBA on DlfA. fSlal1~ .tfee', or rtM on DllBl lftduo.d ohan... In to tal protein (fabl • .., •
. and ftpre 48) and aolubl. prot.1D (Tabl. eo _4 rtpn
SI' ... doouumt.. in the pr ••• nt tu" •• t1S.tlcm.
It CID thua be eOftcludo4 that .,0 ott ... prot.o'lon
asalllat carolnosen-lnduoed change. in all the par .......
studied. Thla prOMotion at inittation 12hu. ot 11_u
oarolno,.1l •• 1 •• q haYe 80" relatlOlllblp With ,be
,~ incidenoe at lat.r etag... Dow do.. MPO aft.o'
thea. ohaoS.. 1. Jet '0 be In.est1sated cd turth ..
• xper'laanta ere to bo QarJ'le4 out to eluclda'. the
aeo:btml .. or prot.ootlon ottered bJ .PO aaalDat DI8A~
induoed canse.. It turther atu41.$ indlcat. tbat lIfO
.e4uc.. t~ hepatQ". .11e! ted 'tty osrcla.ogen(.). tb.n
•• au tbink ot pftol»ln; lnto the •• aot .. obI111 .. of
ita act10n atth. lrlltlatlc:mal phD ••
250
SUPPGnl •• eY14eno •• tor aaoOl'blo 8014 ))a11ll
belptul 111 the tr •• tJletat ot oanceP baYe alr-u4y bea
INt toz-th .". ••• era} In ••• tlsato,.a (C. __ OD and Rotaa,
19?2, Cut_on anel PaullDa, 1~'11, li7t. in&.'I&, li'16,
etlan and PODS. 1~?7). AD 1Dh1bltloD of tor • .,tlon 01
0&l',o1l105_10 Il1tro80 ooapounda from. ..me. and nitJtl' ••
by •• carble aold 1. deaonatl'ated !9. y1trs ~ 1I11'vl.b
.!! .!!::. (lil'72). V1tam1n C 1 .... _,,\dr."Dt of mxe. funot1on oxld" ••• (Coopor. 19611 LaDI.l and Zarlnoni, 1861'.
Levin and 1iautaan, 1961. atau41q_.!l el,.. U~61.
Nga".WIla ot al., 1970. S~n., 197~). Sla,a llD48raok_
(19"') reported that it inhibited tbe coyalent b1a41Da
or the cwro1DOgen. wltb nBA and \hWl a1 ter1lia tb.
Incidence of t~ tGr.-tiona
Sinoe aaoorblc aa14 arta.'. the b1Ddtns of Di8A
nth DBA ODe can upeat It to 1J1duca aoae ObaDae• 1D
the efteo'. or DIIBA 08 'ar •• ' c~l. The pr ••• ' 1D ••• U-satlon w.e wut.,.tak_ 1U) at\14J the .rteat. of ucol"blo
acid on resen.r.'laa llwer and It. lntlu.ace OD DMS,t. ao'loll on varlou.. 4IDQIl8. an4 ll&o1"OaoloCNl ••• blob aQ
81... an Id.. ot the .. chant •• ot .tproteo'lOD slyea '"
the nt-1ft as_mat 'Wartou. oarclnoserl ••
251.
fabla 15 an4 "lave 10 Uluatrat.. the .....
1ft to'~ aoUyl" ot B laroqbt &'00\&, bJ a,001'_10 ac14. Aaoorblc aold br1ns8 about ~ iDol' •••• lDlt1811J aDA then tbe aotl.1 'J 1, tound to b. l"eduoe4 ." 8' aD4 •
hr. Bo....... 1t, heat 'Mble t'rao'lon-BII I, bJaber a'
alIIo,. all tblt lD' .... al. ('faltl. 21 u4 FJaure 1.). tb4t
480..... lD total. BIt &ottYl" at a. enel sa hi' at ...
• urSery app .... to b. becauae or the a.C1' ... .a aJllthe.l.
or It. be., lull. traot1OD RlII which 1a r*,uo.4 ..
all the stud,. mteJ'val. .s.c.pt at. 8 llI' (Table sn .04
FiFe 18). Glucokina.. 1s altO z.ec1\loe4 1D .. 00.-b10
aold.-tr •• t_ aniaal. (liable a3 and It'lalae 22). pp,
actiYit, 1. 81'bttr refiuoea or rUl_lrut<l t&Q.Il, .. e4 1D.
partial11 hapateoioll1 •• d anlllala .tier &.001'1)10 ao14
tr •• tMnt (Table 38 and FlauN £1). Wbel-.... PK la
reduced at all the .t\l4J lD .... yal. (Table 66 and
FiFe 80).
The decre.sed aotlylty ot all th ••• en.,...
Indicat.. a. dec'Naee4 .ate of ~11Col,..18 In ,,00"1. acid treated re,eneratl"! llwer oel1.. 10 other repor'. are a.,.11ab1. em .uch .~1 •• oar,.le4 out with •• corbl0
aol41 1ft 11.'9". Bo •• Y"", Plonte1t .!! al-t (197i) .eported
that 1t did no' att.ot auob gluoo •••• taboll .. ill Jd...,.
252
An lDltla1 laor .... 1. obaeryed 1rl LDB aoelyl" at, ...
.. oerbio aolel la.1e.'lOD (Tabl. 51 anel PiS". M) .1.a hON .... un I, .. ud then atart_ .ed.lac. ., e_ ooapare4 to _tr.a'.d oontrol (parttal17 bepat .. 'a-111__ alee), S. t 1. Nduoe4 fltoa 26 bit onwarct.. ..
lDo .. a.ed aotl:W'lt'J d ..... lID lD ..... ..s .. 8 produ.,s.oa.
oe P-DB abo ••• ,a4Wll deo ..... ID uOOI'blc eo14
treated par'tall, bapateotoalae4 anlaal. ('able 1'1 uad
"lava as) .howl .... eo ... _. ft., .tam.- .\ .eor ••• eeS
81,001,..1. and ,.uo.. phoaphat. pat.bnJ appau- to b.
the _SA .rteot. or HOwb1. ac14. "cleo,. ••• " oar-DB a.'lYlt1 ... lNlt. lD • I'edued left1 ot IADPH wbJ.oh ..,.
be r.ap.aU.l., p.~J at 1_'_ tor the 4.0 ...... " tat"
ac14 .ifttb •• la. !t !!O9 8Jath •• l. ot Q8p..1Jt 1. art ..... .." ,1'11'.,. 8ona40troplD. (<kIpta aad _At ti'5). "til
\be ••• 11abl. elata, DO o0b01W11cm OaD 'be Md. "·saP41aa the a.bal. of aaUoa ot uool'b10 .014.
JIallc • .,_ (fabl •• 3 an4 Plpe .1'.) abO •• aD
lDltlal bo ..... tollo .... ., •• 1pt.tloaat Mo ..... lD
.eatm ... ttna .0.' 11... at.." uocrb!o ao14 ••• tilMll'.
An lnlUal Saar •••• in tM a.tlyl" app .... -. be
UOOJ"blo ..,14 .~1IN1u.. 1Ift' ••• , ~ 4MHue a' 1.'. lo .... ftl. II&J be rela'" to tit. 4Mr ... - qatheala
253
broUSb' .bout bJ t1M alyen do.. ot ._OJIbl. ac14 or
IIQ b. &I. to ooafl,..'lODal .1'1.... att_ _orblo ac14 a4llS.D1a""."loa.
!be d.or.... 10 all th... eo.,.. aotl91tl., .., 'be 4u. '0 the iaor ... ed p .... bl11t' of lDtel"lle41.' ••
or cia-at. tbrouab 'he oell and II1toohoncSp.1al. .. b ......
rotal DlI. OOI'l' .. \t~ 1. 4.0 ...... ed 1D part1aU,. hapatecto-
ala. aI •• l. -, a8OO,.bl0 ao14 (1'.-.1. Ie MlCt Pip- .. ). !ht. 4.or.... I, ,a4ual ed toUlleS to be aaa1lNa .,
"It hr. !bt. can be ooJ'l'e1a1;e4 .l~ the braakina aoUon
of aaoorba_ OIl Duel.10 acld. ... 4eIIouv.,_ bJ OIIuPa .!! al. (10'18). !b. pr ••• n' 1M •• tlsa,10ll alao ooI1f1 .... the p:r.noua report. Ira. our leer.torr (Dblt a. Rao. 1880). O\U' .. eau1 t. ... in 8004 a,HMftt w1" tho •• of Bbl ••• l !l al,lr (10?O). o-r • .!l at. (1913),
(10'1') &D4 OY ..... !1.!!.:. (18'11), Bleha!1.!l.:. (10'1&)
11110 01.1 .. 4 that 91taalD 0 .., b. l.Dyol..,.s 1ft •• ""'dlna
n80p1 •• tl0 0.11 prolU".'IOll .. 1t 44101"."_ tb .....
or DJlA I,Dtb •• I. 1D tuIIor •• U liDe.. Vl'UIln 0 al.o mor ..... trapent.t1on or DBA bJ Wlaoha4\ll_ t8A
rep"'" an4 ohP~.... (st1oh.!! a1... lG""). !bi. gowth
... , .. Aba Pl'oper\7 of .1tamlD C baa lot • 100d
oorr.latloDabip with ~ ob.~.tloft. ot Lew1D (18~')
u4 'l'la4al.. (1W16-) wbo .epos-tea that aso_bl0 .014 ao ••
254
.. • r •• .ralbl. lDb1bltor or oAMP pbo.pbodl •• '~ ... and tim. aAIIP 1.8 lnor .... (Sek •• l u4 "baler, liSi)
whloh ults..t~l ro •• ulta 1n aD lfthlbltlon ot .Uul ..
~"b.
t't*al pro,.iD OOllhnt (7.1:»le .,a aD4 Pl, ... 60)
paaln. alpUloanU, unlllup4tt! at,. • .. orblo aclt
tr.atMnt ...... ao101. prot.iD oontent 1. uauaUr 4.or ... _ ('fable 81 and 'lpre It) at'ep uoorblo aold
a.lal,"'a,loll to p .. 'lal11 bepa, .. toatMCl aDlaala.
Thi. I. or lnt.r •• , to DOte tba, aU t.b.e eD.,'" .... areA 1r:t the p,. •• ent •• '1 •• or .,xpers.unts, .... 1D
the soluble traotlOll. !be 4 ...... Ia ... lou • ..,ate
aott"I'l •• .., ~eretor. -. ,.el.'.d .. tMOftJ'all 4_ ••• 04 a,..ttu.al. 1D .ol\\_~ pl'OtaD 01' .'s..ula'ecl
o ... bol10 path.., ot pro,.tD " a.corbio acid.
To etudJ the .tteo' of the .1'aat.a OD Dea-
1n4uoe4 bSochealoal ahua •• l' wa. gSYeI1 to ...... with
the OBtolllopn to p .. 'lall, h.p.'"~a1.e4 aD1aala. All the.. ena,.. will be 41,cna •• " be.. 1D ,bt ...... ..
kbl. 16 IIft4 111F' 10 Pow tha' .. oOJdtlDa. trea''''' ot o..olDDsen and vlt..tb 4.or .... st~ ac'lyl" of HI "t It 1 •• uch 1 ••• ~Ul the, ob ... e4 Sa DOA
255
tr.ated poup. !It>> 4.0,... .. \. In thl. poup r ..... I
bet ••• n R-18 per a .. ' wb .. ~u. 1D DQA-V •• t.4 eJaal.. the 4.0N... oba"Ya4 1. abq,ut 35-'18 per oertt.
\
fbe:ret'OI"a .. aaa $ba' uoar"'ro uld wban 81"' •• lUi
'DltBA I, siYing a .. Pl"Oteotl. whan total B 1. takeD . Iftto account. !'he deor.... ~b.U'.414 1D. this 8l'oup ..,
I
luat bo •• oorblo ac14'. 0.0 .tto.' wblOb .. , not be
toxic to the o.U.
SJa11ar proteo'SOD Sit ob ...... e4 10 ~ b •• ' .bbl. ,
traoclcm or baXOk1Da ..... UJa i ' Wbaft tb~ two , •• , ohaaloala I
wer. alY4m tOlether, t_ aoUyltJ 1. tound '0 b •• Dbanod
and the 4.0 ....... , wb10h D1mA wins' abollt __ ,1.-
alOM, 1. DOt UDU •• ,-, ., aDI of the at.udJ iD, .... ala
(Table 21 and Plpr. ")'. 'Cab .. ob,,,.1 that DKJt.l-
lnduoed oban, •• 1n HIt 18 coun'er .. '" upon __ •• 00rbl0
801d. so •• "er, BIll I, DOt auoh 1DtlutDoe4. Tlw
4eere... 1D. UII utlyl tJ app...,o b. ouaulatl •• 'tnt.t
.'111 •• GOti.e that qala. the deol'" ••••• b .... ect 1D
thi. groUP of anlilal. alve • oOlll»lne4 creaeMG' ...
1..... (Table 8'1 aDd Pl.,._ 18) thaD \bat ob •• r.e4 lD
DaBA-w.ated aroup ('1&1»1_ 26).
Gluook1n&s. aot1yl" &lao re&1-'''' a .s.11~ kind of pattern. 'lb_ aotl."ltJ 1. DOt aJ.plt10aa.tl,
258
alter" in the. _ta.:1. 81 .. " • OO1IbS"a4 tp ..... , of
'M .ltala a. oarol_,en (!fabl. &3 ad "18\11". 28).
W. ..a th.t DliBA elM...... OK actl.", I.D r ••• neraUDa 11 • ., anet tb.l. ution of I)_A 1. oollD' .. a.'''' ., •• oorbl0
acid "a.taen'.
PPK I, .110 .11111 .. 1, atteet*, ." ucorblc •• 14
and DJIBA tr.atunt. !'.\tl. Ii anA Pipe ae mow _._ 1M
tho 4ecre ... In ,he .0,. aot1Yl',. bro\llbt about ..,
01181. lD r.seneratq 11 ... I, Jla4uoe4 or nta1l1tl-.l mea
•• cerbl0 ao14 .ea stye tr1th tbl ••
'1.,11 «6 anA Pipe ao abow that 1;bou&h ,It aotl'11tJ I, reduoed in the _wale pyen • ooab1M4
tr .. t1Iel1t or tM two , •• , cbe1l1cal •• tha eatent of
4eor.... 1. auob 1... than wha' •• I\Otlo. 1ft DISA ••• te. partlall, bepatMtoatae4 &roUP.
ShU ... prot.oUOD .... oorblo ac14 1. or, ... &law' DJlBA-1D4uotM! obaDa" ill LDB eD&7- 1D ...........
tiDS 11.er (Table 61 .-4 Plpr. St).
Uallka .:1.1 the.. ..,.... the att .. , of tI01ib1rM4
.... tMntl ot adOpbio ao14 an4 ,he 0 ... lao8- app •• -
to ba OllJIUl.t;l.e aft.' ot the ,., 011 oep..DB ('fable fI1
.,,4 Pla"" at). 10 pl"oteotlOD 1. on .... '" .. oor\)10
a01el 1Il tbl. • ....
257
Bow •••• Mallo ttUJIl. &1ao abow •• trd in tbe
en., •• aot1 .. 1t, .a .bown bJ the .USI ••• ot 81,oolJ*1, and ••••• that •• 00I'lIl0 ac1d e1the reduce. \he att.o'
ot IItBA 'a' 8. 11 and 84 br) or total17 D1l1Ul... The
aotin'7 r • ..s.n. 1nalp1tioaJltl" u, .. .a ., aa aD4 '2 br
(Ta~. 63 and Fl~. '9).
!bue, •• olla.... that uoo,.\)10 acid pl"o'"'. tlle Qat .. t'ro. toxic efteat. ot DIBA 117 p,~uo1n& or cout ... ''-ao'1Da 1ta eft.ot. on the en.,. •• or &17001,al. and _110 en.,... 110 fltteat on CMF-DB.., !Ddlo.'. tbat
aacorbl0 acid Gould bl'1na 8011. oont1l'aa'lonal. cab ....
In the 1.0., ••• ot the _.,-. tbl total aottvlt,. thua
belns unarteote4.
Itt.at. ot a.corbl0 ac14 on D¥BA-~a-' ohaQI ••
in DBA are illuatrated 1D fabl. 68 aDd itllure 41. ••
oan .,lauall •• \bat DO pJlO,"'loft 1. oltered a&a1D.,
nasA-indUced ohanS.' in DJtA oontent anA the d ....... .
m the 1e ... 1 fta ad41tl.e. !be r •• ult. ar. la
oontSra1tJ with our pr.noua repon. (Dixl' and Baa.
liBO) wben •• do not obaerv. aDJ prot .. "- .ye t111
1& 4a,.. at ... partial bepateotOllJ-
table '18 and 'sa .. a 60 Pow tba' tbe total proteiD
OOl\hn~ 111 the animal. 61 •• 0 a __ 1M4 .... taA' of
258
.1'.1ft and oarolnog.a 1a DOt a1sn1t1otAftU, cball8 ••
• hE cOISPared to pwUaU, bopateetoal._ coatJtol.
'lb. deorea.eel protelrl oont8Dt att .. DJiBA Reatlleftt
(ot. "able '13) 1. broUSb\ about to alaoat DOrlial 1 ..... 1
when uoorblc 6014 1. stYeD toaotb .. with 1'_ !l»
lnaN... ill protein cofttent II&J b. beoav.. of an
Inoreaaa4 aliA COD'ent ".poJ"ted earll.. 'DW, anel RIO,
1980).
Soluble protem oontent 15 tound to be 4.on ....
in the .. oup of an1aaltl 81.-.& coablne4 tl' •• taent ot &800I"bl0 acid and DIISA but Itt.. dearea •• tS to • 1 .....
... tent (!able 61 and FlguPe &4) than 1~ 1. Nduoe4 1.
DUA v.a'ed partiall, h.p.'Htoalae4 an1aala (Tabla ?'8).
Asato a proteoUon ortord. 'OJ .scarblc ao14 ... 1Da.
DIIBA-lDduced ohana.. In proteiD 1a •• 1 la d.-matl-ate4.
par.ul!DM or •• tl-.Mol ""' wlSbd£awal. of •• !itadlal
OIl pllBA:lrfiuol! bloch.loal, eW'! &D ,rM!!!£1\1M
110\1 •• ,).1 ... ,
x.tJ:log8ft baa been report.4 to aot .. • prOMMl'
ot 11 • .,. oaJ'os...o8~.ta (BaUla.!1!.!:., W'13. Laoaleap-
• .. ale li'18. bu' it 1. not kD01'f1l tbat tftat1;ller eatrOleD ~ ... -' .~
25~}
1
it •• lf ut •••• oaP01llo •• OP .t-lImlah. a pr_xl.,Sna iD1tlated oeolD •• ll1o 0.11. 0\11' lnt .... , ... to atu4J
the 1ntluenoe of •• 1:I>&4iol OIl DUB .... lDduoed. bloohCill1oal.
chang •• el101t_ in ,. ...... '1111 aou •• l1v .. 4Yl'1D8 the
ln1tlat1onal pba& .. ot obeldoal OAroll'logeuea1a. Alao •
•• wmte4 ~o know wbothC" ablation or the 0'1'.., (b.ec.
a\lbatantlal reduotion 10 the .,tros_ 1 ••• 1) wo\Ud
att00t ~. b1oCbemioal pro£ll. 1ft tbe ~.8.nar.'1Da 11 var expoaed or unoxpoeecl to 1me ouoll1Ol_.
'lable 16 and Flauro 11 .how that oxoGenoU.S
•• tradlol Induce. a ara4ual 1ncrG .... 1ft 81. -.uvlt7
.ben £lYeD at ... PaP,tal hap.teoto., a4 tbeD i.
reduced alp1tloant17 at,.. 24 bl'-. Aft 1I10HaaM
aotl.1t,. of BK polnt. out to aD enbUlOed :raM ot 811001,..1.. Slll11ar1J Dl I, al.o att'eoh4 (fable II
an4 PlaUr. 1&). How ..... haat labU. traG.lao BIll
abow •• de." .... ill the ",{wit, aru .. 16 bJa ODlJ -.Il, oOllPU'.4 to p .. tlall, hap.teotoalaed eoa,,"l (!fable 28
an4 nFe Ii). A 4ecrea.a at lat. lnteryal. app ....
to be teed back 1l'lh1'blt1cm of 1l.xok1n.... !h1 • • tt •• ,
of e.trad1ol 18 like ita .ttao' on .... .., tu.ora (HUt .!.i.!L., H166, 19~10il). In llol'1lOlle depan4ent
••• ." tuMOra, aclJaSnl.v.'lOD 01' pharaacoloa1oal.
00 ••• or oatroSeD pro4uoe4 ah lftOr.... tD the •• ,'Y1"
260
In tb ..... au.,_. Oluook1ll .... 1. tlr.' 1ftv ... e4
., 8 hi' _4 then deor ••• -' 1ft •• tra4101 ....... '.4
anJaala when coapare4 to _tr.ated part1allJ hepa.'o-
111." aa1mal. ("abl. at an4 Flaur. 23). PH ahow.
el 1nor .... ht_ 16 bl" after an 1nl~la1 oOP .... a'
S. bp (Tabl •• 0 am\ lf1~r. 27). !lb. aotiv1ty coa. down to c.ontrol lffYe1at '72 hit in oltradiol-tr ... tea an1ma.llh Similar- 1"eport. b ..... b.en put ro~tIl bJ HUt
Gel hl. co-one •• (1~., 1970.) In ~y turo...ora. i)TUYate kiM •• actiylt} ebanse. In a 41ft.ret ftll'lMr
(:rab13 " and l+'~e 31). Flr.t It 18 decreased and
then 6I'ad\1ell, lnor.a. •• " reaoblna I. t& ~. ., 2. hr
and then agam .'u~l"t.6 oOlL1ng down '0 • le.~ ccapu-abl& to that til par't.allJ hapatooWla1.e4 control.
at '2 hr. As tta. tUltlo1pat(;4. HI. PP!~ anc1 n all show
an lncv.~&e4 aotlvity .tt.r ~strQ~l101 ~Ql.tpa'lQD. An inltial !ncr'&&8e in t.he •• tmsymall at low loDlo
.tr6J)8t.h Call b. lnt .. pr.t84 b7 aD 1nc ..... til ,-aot1vlty of the t.-plate ~ •• pon81ble tor their aJD'h •• l1
01' bJ • .1\ aot! •• '1"" tJt tbe aol.oul •• abed, -6as-a sa the proo ••• ot '~ansorlptlO1l'" •• tratUol. l' b .. be. l'eport4t4 tbat u: 11$ 11 .... ·1$ not .ct. 41._..., or ho.-,aal control patb~ tbe • .,._ gluQokta ... ,how •
• 1gnU."loan\ al teratloa8 la l'aapone6 to ohana.' 1D the
261
lI11S.eu .1~ the bod (Parina 5 ~.. 1068, ~ .. _
.!! &1., 1"3). How .... , 1D eontradlo'lOD to abo"e report. both HI and OK .... lhow1n& .1aUar tltan4 10
regeft.r.tlns liver "'ep •• tradiol ad~.tr.tlOD.
LOU alae shows & conllatantly inor.4aed actl.lt7 in
res.-aeratlng liver art .. estradiol treatmdt. (Table 62
and Fisure 35). In ~y glnnts (normal. or cano.roua)
.l, SI). LDa ••• ".ported \0 be _l ••• teet In r.spoD" to
the a4aaln1.tr.'lon of •• tradlo1 (Mchard.. aDd 1l11t,
1978). !'b1. iDOl" •••• ~ b. duo to an In~.u. in
cert.iIl laoQQ epeol •• or the .n~.. induoed bJ boraou.
Etteo'. or eatradiol on 00 '-DB 1D rq ... ".claa liver are or lfltu'eat. Table 5& and FiFe H abow "'.,
when coapared to untr.ated partially hep.,eotoJll ...
ent.aala, •• tradiol-tr.ated an1aala abow aft iDo ••••• ,
level ot thi. en.., .. at e br whioh 00 •• 40wn to •
very low leval at lfl Dr and 'bm start. ",a4l&8111 1ncreaslng oosa1ng to u.l,a)at control leve1a. LS.Jra um, 06 P-tnB 1. alao rep01"'ted to be increased 1n --.., &1anda (R1ehaN.. and 1111t, 19'12). Uterin. 05P-DH 1a
increased in ovarieot0lS1aed rats 1D r •• porlM to lnwaveflOu8 aCJmD1$tr&tlO1l of estradiol 'aal\b aDIl
Barker. 19'14). Lt. ... OI5P-DB .... pen .. So t ... pS" .....
• ,\14, ~o •• ua4101 adll1nlatr.'lon 1. --err Bob. l1D
262
"t.l_ 08"00 •• l"epo:rtH bJ SIIlth and larJwt (187t).
Stu41 •• of 6ekeJ'l (l~S') b.a •• auaC •• te4 tbe _sl.'.nce or • trana .. lptlonftl aeobanl. tor the CODtJ'ol of
uf:lers.n. 06P-OO. A .1II11e '.eohanl_ appe ... to ul.' In 11" .. a180 wblob ••• ulte4 ill IQ'l iDe ..... eotiYlt}
of 08P-DB 1n ".pnal'ntoa 11" ...
Iallo 0)1&1- (*!abl. It and Flgur. 43) ... gl.t ...
m initial. incNf1Se followed bJ • (teoIt",_ after
•• tra41ol. a4a1'l1.~"tlO1l to p.r~1.U7 llep .. teotoJda..s
.s.c.. 1ft) othor r.-port. 111"8 .. "all able OIl tbls en&J-
end lnere •• 84 activity or ftAl1~ enS7~ -usa •• '. CD
:lncpeaaecl p~od\lotlcm Of' redue4ld.",r141n9 nuoleot14.
uaed •• a .orector in ,.ttr Acid .,~th •• l. or prot.1D
qnth •• l.. '1'$11. lnYfrat1ga:t1c.'U 1a 1ft .&1' ....... , with
the 11n<.11na" ot .w,lf' !l.!l:. (19'11) .b() r.,ortitd a
4.0I·.aaed mal10 enaYU6 aet1v1tr in ml2lMUt1 glan4. att.
oatrogen ~ltharaval caused b, ovarleot~.
Total DNA aout.at 1. rtl4uce4 in ,,_tl&11,
hepnteotoat. •• 4 anlaala att .. eatra4101 .s_SaS.watloa (Table 170 and Figu.t". "). This .ttee. of ..... 4101 lD.
ll"'(j~ lea unlike Oft otb.,. ti ....... 1a eado_tltl,.. l'
14f ro})Orted ~ stllallate mlA .,ntbeal. (Klana. AD4
wOl'J8elJ. 19131 1.,8.!! e1 ••• 19'1a). Bouy ... a total. J
lDblbltlOJl waa ftotlce4 lD endoaetrlal O ..... lDOU
(Genalatll, li?6) aDct 1ft aIIl~' oyarian tauIol-.
263
10 .1 WO (Darwlp, lW78). Tbl. 4eGr.... lD total WI.
COD' .. ' aq be the r •• ult. ot •• qu_c. ot •• eN
ooours.na f'roa the enw, of .' .. olda to It • ."ent'iaal ••• oolation wltla ratel .... cbrOliattn (I.a •• , al, •• l;as,
)leana aD4 O'Mall." 10'12, SbJtad •• , al •• ·18'12) .. --D •• pit. the .v1ld.ne eftect. of •• tropa adaiDl ..
trat;lon on 11... DIA, 1t baa 110 tal' 1'_IDM \aDol ...
*-tIler thl. I\1ppzt •• aloD .eflect. a cUreat eftee' or the bearaoae OIl the bepatoo7'. or .be~.. iD.'.a' Dlj,
Q'Dthe.l. oe .... beoau •• ot ebans_. reaultlq tl'Oll
eft.,. or the boMIOne a' other .It •• Sa tb la"'.' IIftblal. Th •• eoh&lll_ bJ wblob *1. b.or1IODe lab!lt!,
DRA .'ft~.b In dUrerent 'l •• u ..... U1lkDo1m aM
1 •• tId IIQ 41t~ttP fro-. one 0.11 .,pe to aDOth ...
fotal prot.iD eem'eD' ('I'abl. va and PJ.au'Pe 61) _4
801u\)1. protela eo.en' (Tabl. e2 _4 Pi6ve 56) .... 0
low .. Ol' IDalSD1tlo_", alt .. _ 111 •• "'&4101 .... tea par'lall), bepateo'-l.e4 aataala ft_ 00IIP.r- '0 un .... ted control.. '1'Jma," app.... tba' re4uoU-
SA DJlA OOIl-.n, i_.ect 'b7 ~. boJ'''- in tiM pr ••• '
264
.,..,- 1. attaDded bJ an 0'¥ .. &11 PeducUOIl of pstoteta
afnt'b •• l. which • ., PPCllPtl, .e.1.alt hl 0811 d •• th all4
'I ••• t.a.olutloa. 'lbi. 4aor •••• 1D proteID con'" -, all10 b. clu. to an lnduoed act191" of ao14
pro •• ln ••• 01' b ... v. •• of 1ta .tree'. 011 alA Qat ... ld_
.n.,.... our I' •• ult. are In .upper' or ••• ~1."1 *D4
a •• 1I01l (19V2) who r.por .... .xl .xponentlal lDoz' •••• 1ft
the app ........ or pla 8M protein at, .. the tft •• tun, ot 11 .... with aD ._1 del'I •• 'lv. or •• vone. 2btt
4.01' •••• 1n ~tal and aolubl. protein CODtet which
we oba ••• att .. 8 br IIaJ b. beo.ua. or the w.a.,.,t or theae .,ntb •• lae4 pl .... prot.taa fro. liver to pl .....
Aa ..... 4 to tl» etteo.'. of ••• 0S ... u4 DUA 10 r.a-•• tlna aoua. 11,..,. _4 1t. Wi ... OIl rJMBA..
lnduo.,d ohal:lge., •• VoS8n 1. toUQd. to p.r' ItO" ette.t
on DMBA'a ao'iOll 011 " ... 10U8 •• ,... an4 l' GoUld I'.YOk.
DMBA-1D4uoe4 low .oUvlt1 •• of .-10\11 eas, ... l1ka WU_
(Table 16 a4 PlaUN 11). !'bough tbe .. Uylt, .... ia
1IIl&l' .. e4~ lalt;lall" the alpUl.aDt d .. r .... at ..
2. br 1. 1... than. .bat;. ... ob..... ill DBA. w •• , •• 8I'oup. It app .... U1afJ W8J.-lrlcluoed deer .... 10 tbe
.-1. 1. oOUllte'racla4 \Q' •• "a4101. 8bdlar efte.' ot •• tra4101 I.. DOtloed OIl HKl (4fable 21 aD4 Pi.,.. 15),
285
BKIl (Tabl. 28 anel Pip .... 10). Olt (Table ... aD4
Figure 2:5) em DQA-ltl4uoe4 oba1g •• 1ft th •••• .,.. ••
It 1. alao to'GDd to ha ... e .. Protective .tfect •• taP. •• PPK 1. ocmeeme4 (Tabla 40 and l'f.auPe 27).
!be. etree' of tb. two cbealoala Sa par'taU, hepateotoalae4 an1aal. OD IX. (fabl. .. a4 'laur. a1) a4 Lml (Table 12 aDd Pf.aur. a&) allG Ulua"a' •• oount ... ert .. , of ..... &4101 Oil naA.
The ohang •• 1ft 06P-DB ao'i ... lt~7 (2ab1.68 _4
FlSW. 89) in tbl. Sl'OUP or auJaal. are IDt.e •• tlft8 i;o
not.. •• notioe ~t ooablne4 tre.ta.nt of' til. horIIou
and the oaro11JO,an .1 thu' tmha... ,bet ""Y1" o. ra..tnl unett.atl..... The Ino....... 1ft the aot1'1'1'7 1. IlUCh .... pro.bum' tban It 1. sa •• tra41ol-v ... ,,,
aroup. Till. 1110,.. ....... to b. becaua. tit the
1I10"&1_tl0 efteo' of the '110 t •• t ebealoal ••
Bo........ aal10 -Sf" 40.. Dot DOW &OJ prot.otlea
bJ •• tra4101 .. dn.' DOA -lDduoe4 4 .. r .... III ".
aotlyltJ (Tabl. et aDd. "laura 41). Tho ••• Voa-w1_a abou' .. in ..... in tbt &0"'1'1_ 1D1"all1 at S and 11 br. the aotlYlq in 'the poup of aaS •• la a1y.
a ooab1Dec1 tr.at.ent of the bOI'JlODe and. oarolDOleD ,. ••• lD •
• 1p1tlontl, reduoed at alaoa' &11 tb. 111 .... &1 ••
266
Btta.t, . of the oollblned tr •• t .. , ot tha two
ob..soal. Oft DBA (Table '0 uti Plaure .') abo. that
the two t.at Gh .. teala, oU'o1llogen and hol'ao_. ..Sill about • .!gn1tloant deer'", 1ft ~. nBA le •• 1 .~D SiYeD alorut or In coab1l1atlora. ID the P'OUP r ... 1YlDa
• 008111*" tr •• ta.i or tbe two, t_ •....... ob •• y.4
1. ot add! '1... nature.
Total ~,.lD oo"'-t (Tabl. ,a ad "law. &1)
al.o .bowl th. __ trend •• DBA do... l' 1. 4eor .....
all tbl'oush the .t. s.u .... a1. 1ft 'hle &rOUp ot
anlul.. aDd •• vosen 1. DDt tound to be ett.otlvl ." ..
DIBA. bpJ'181ftSl" ... .,101 ... 'a • protectl ..
ett.at -saina' DIBA-ln4v.oe4 4.op •••• 1ft .olUble FoWIl OOD'et (".ble 88 _4 PIFe &&). ftIouah •• tracllol
briDal abou.\ • 4ee ••••• 1ft tbe aolubleprote1n OOD' .... '
a •• _tI .,2 bit .hen aty- alone. an el .... ted. 1 ... 1 ot .01.1. Pl'O,.lD 1. ob._ned wlutll it ... at •• with DBA.
1hl. ett.ot or the bOl'aOM 1. _tut&oa1.~le .. oov.l.d. ...
beoau •• ot an lnOJte .. .s. RNA pol,aer ... ao'191".
It appeU"a that the •• chillS.' brollSht aboU' ..
DIISA.., ha •••• e rela'lOD .1~ ,be !acld ... of
hepatoaaa. Tbe do •• la tbe pr •• mt lDY •• ,q.,lOD. how • ., ... 1. auch hlgh .. (0.& ..vq bo4J -lah') tbe
26'{
,l •• D bJ other In .... t1aatora (hper, li7&) eo , ..... .. a1.t1 .... 1,. low .. do... (raft&1n& 'bet ••• D 0.088 .. ..
0.1 -slq ~od, •• s.pt) aftd found tb., It .... \ll ... 1D
the de .. elopaen' ot httpaioaa.
It ba. al •• tIdJ be. .hown _ 1OD"_1 -.4
Sotwllea1 (1.9) that lar •• do ••• of •• Woe-- 0_. 110 peJ"llMen' d ... S. ill l1v .... 11a _it tbat tat. 11 ....
s.. able to dapt to tbe "Dthe'lo .'.0,... !her.tor •• the chana •• we ob...... lD th. pr ••• t w •• tse.'loft ..,. or ..,. DOt h • .,. &nJ re1atlonldUp wl tb 'Gh. tu.Ir 1noIctlDo ••
Further experS&mt. a' later .tas •• .., illustrat. It • ••• oolatlon 81tb hepatooarc1Doleneal8 and ,ban .. obaDl .. ot •• v-dial •• Uon -ould btl ••• ler to fellow on DIIBA-
1I14uo.d 'blocbDloal. chana'. 1n the pre •• t In ..... 'ta.tl_.
OWarlecto., ot alo. re.ult. tD eba ab.eno •• ~
•• tradlol lD the bo47 ana the .tteot. ot tbt. ~Dal .1tbcht •• al .., naw. t SA a1 'er.'lOft la the _.101017 of
11.... O'farl.o\OWIJ (fabl. 1'1 _el Fl.pJta 12) ... aulH4 1 •
• p'a4ua1 m4 dcnJ.tloant a.O? ... 1ft total HI aot1 ... 1', 1D reaCleJ"atlna 11.,.,. t111 2.4 br wb10b 1a'-' on start ..
1" •• toI'1DI 'but .tUl 1" ... 1_4 as.pSf 10mtlJ low..- tbaD
~.t of pU'Uall, hepa, ... al ... aDl_1. wS.tb lfttuao'
26B
0 ..... 1... 10 .uch repor' 1. ea11abl. dea11D& with 'h.
ett"'a of o ... le0"-l_ Ho...... 6D coatra.t to 'bla. Hllt and hi. cow.bre •• pOI"" aft w..... 1& SK
"".it} 1rl DIBA-1D4uoed __ arr cuo1rloaa. .... DOA
... g1yeJ'1 to the •• _laala, the aot1.1t1 ... 4eo~ •••••
lul*tber at all the lDtG'yala. It allow. \hat o.arl~to., 1. att.ulatlns PMBA'. aation " 4eor ••• 1Qa tb. a.tl.stl of' the enq_ to • 11' •• '''- extent ('lable 1" ..
FI,ur. 18).
Plpr. 18 mel ~.bl. 18 Ibow that ••• a4101
ada1nlatJIatloD to ttua.. 0 ... 1"'0111._ , .. tlal1, bepa-tectold.ae4 an_ala, r.ator •• the &0'1-.1",. Alao lD
DIDA-treated oyarl •• toJd. .. ct-p ... staJ,lJ bepa'''~ud
aSaala, ... &4101 .1 .... t.d the aotlylt7 .en oOllPAI" •• to 0'9'01.oto.l .. 4 anSaala undeaon. partial h.p.'eo~.,.
It appe ... a ,bat tbe .tt.ot b%'O\1ght about bJ o .... leotolll
ar. r •• torid to 110 .... 1 bJ NOS'-"' ••• tractlol.
a.at atable tr •• ,1.oD ot U l.e. BIl - ___ all,
to\lDd to b. deor •••• .tMlt par'l~ hepa\eoto., 01 oyarleotclJl1 •• d ant.ls (Table 2S awl Pia •• 11). all
alao a'howM • 4....... tat ... partial h.pat.otoIQ of ,-an1l1&la wi tb abla_d 0.,.,.1.. «'table 10 an4 Fl&v. 20).
~I'etor., the to'al deo,..... 1n U -" Yl\7 .., '-
attributed to • auppl' ••• lon ot it. lao.,-__ .... tJta41.o1
rao9al. Dt.mA treatment brought about .. ,-\b ••
deo~.... in ovarleotoat •• 4-partlall, bepateoto.t ••• elaala In both the 1.0.,., ... un (fabl. U •• ,. .....
16) and un (Table ~ ADd '1". 20). !he "eer •••• 18
toWCl to b. act41 il.. 1D nat ....
then •• Wedlo). I, alyen to partiall7 bepat_to.
lI1aed-o.lIJ"leotoalstKl anlaala It m1D1a1 ••• \he .tt., of
oyarlecto., In botb the IlOeft.",. of BX.(7al>l.~h. 80
and Plpr.~16, 20). DImA .xpoeure of th ••• partlall7
hepateotoa1aed anlaal, with ablated 0 ... .,.1 •• -.n ,I,. • • XOS.nou. ..tradl01, rewl tee In an iMPe... lD tlw
aotl.1ty or ma which attalDa the oODa-ol 10.,.1 .,
2t b1' (fable 2' and Pigure 1S). Bo •• yer. alII _
in1tial1,. " .. Hued toUowed bJ an iftCP .... '111 Ii br.
ABaln • deare ••• 1. IIOtlo_ ,-table :SO &114 .ripe 20).
!bt, oet-talDl7 tho •• tha~ OIISA lftouoel eo .. 18oa,.s.c
al, ... tlona in the .nq ..... t ,he Snt.rvala BBI 1.
lI&X1aum or enbanoed, BIll Ie cl.er .... ". At. 2' m-•• 1"1.. 1n 'both the • .,... .., b. HO".. of .tl.alaUOD or the pM. Tbipet01"., w. •.• til., .... &6101 v •• t ..... , ~11 reduces or ~pp~..... ~ .,teot of DlBA .at
o ... laoto.,.
270
, UDl1ke H. OK reu1 .. 4 hiaher ., .,., of ,be
II1'eryal.. Iftore •• ed OX acttytt, rav.al. an Snor .... 4
u'Ula.'loa of a1uoo .. 1n par'1all, be.p.teo~aS. .. .
en_ala· bj the o ..... l .. toIIJ. In DDA-v •• te4 POUP ot partl811,. bep.'..,'oalae4 ... d.ala with abla'.d oy .. 1 •••
,be ohana. 1a tbe uti 91t, ot OK b oUlNlatl... .tteo'
ot the 'wo .... t!Mnt. when ooapee4 to " .. 'lallJ
hepatectoll1sed c1a&1. (Tabla 36 aaS. Flgure 8.).
Estradiol a4alnlatratloD to the •• oyU'"lectolll .. 4-
paP'tal17 hepateotclll1 .. cl _la.i. oauee4 a 1uJ'~
in ...... in OJ{ aot191t, (Table as and 'ipe 8t) _eD
compa:red to the ettect. ot oyarlectoar 11l partla11,
hepatectoldce4 cmlllal.. Bow.wer, wlwn »MBA ... a1 .....
•• trad101 1s to\llld to be 1... effectt.. •• l' ...
aotlod to be 1ft 0... ot HI..
Partial hap.tecto., of oYarleotoadwe4 ant.ala
re.ul ted 1n a saMra), 10 •• of oth81" ena1". D~' PPK
(table 61 ana Plaure 2S). PX (!able .'1 and np- 32),
LDB (-la"'l. 63 and P1SV. Ie), oar-DB (Tabla S aD4
Piau" •• 0» ua .al10 81l1lJ- (fable 65 ancl Plaur· ").
Stallar J-e4UOtIOD in all the.e .D.,.... 1. "epaI'M« '" B11t _4 hi. eoworker. (18'10b) 10 DliBA-1D.4uM4 -.arr ouolao •• b:I o .... l.otoaJ. 'lb ...... e.14'. are al.o ill
line with the ob.ervatlons "that exogenoua •• tra4101 br1n.sa about an ln~ft.alJe 1ft tho en., me act!v1 t1 1Il tbe
pr •• ent !n ••• t1Satlon and previoua l-aport. (Richard.
and Htlt, 19?k') in n~)J~aal br •• at an4 br.nt ~ ••
With DEA alao. ovarleoto., r •• ultecl 1 ... t"urtbeP
reduotlon 1ft t~ en.,.. aotlYlt,r. !be .ttact .... .
tound to be add! tl ". 111 nat\D'e in all the abo.. a.-•. PPK and PIt .... enlWl0e4 1Il ........ \1118 11ftii'
In .e.ponse to •• tra4101 a4a1D1.trat1oD to o ... 1 .. ~1 .. 4
e.1aala (PFJt -Tlbl •• 8 anel P1gur. 28. Pit - 1*1. fa aDd
'lgure 32). It I, aleo deaoDJItraie4 1n th ••• kbl •• aad
Plaure • that auppr ••• l". aotlan ot D1481 and o •• leoh.,
Ie re4uoe4 b7 ellwa4101 aM tbe actlyltJ uau.al1, r • ..s.n.a higher ... n at'er a4.tftl.tr.~loD of DMBA to tbe ••
ovarleotoll1.- partlaU, bepateotollluCl anlllala -bell
oompared to resenerat1na liver wlthout Cl, otb ••
tIt ••• en'_ Bowe.,et'" DO as.pUtoot ehaqe 1a ob...,. •• &
In LDB aotlY1tl att .... trad101 admlrd.tr.'loll to
o't'ar1eotOlll .. 4 ""'partial17 bepateotoalaed 8,,1_1. wS'b
or wl .. thO\lt DI8A " •• blont (Table 56 and ngure ~). !be
percent as. ..ILl u.. rell81ne4 lower' 1B both tlw p0uP8.
oe'.DB .. u DO~ found to I"eator. 1'. uttyl" lD
lty .. .rter •• \'r&4101 adas.D1.tra,loft to o ... 1 .. ~a1 .. 4
272
mbaal •• (Tabl. eo .,,1 "laura 40). It _ 4ear ••••• at aU the lDtarvala -bin OOlipare4 to Wltrute4
partiall, bepateotoalse4 oOlltrollf. Th1. bahaylov of
05P-DB 1. unlltre uterine OSP.DB whioh r •• t .... !ta
DONalo, att.. ..tl'a4101 tr •• tJIerlt; of o.arl •• t;OJd.aec\
&D1IIala (SaS.th and nal'keP. 18V.).
ao •• YQ'. with DlmA. the honaone •• ta4 10 _
ant-sonlatl0 llaIlnar and tb. .0 tlv1 tJ .1the r".S,.t alp1tlc&J2tl, _alter_ or reduoe" to a aaall.- extea' than it .a, in miBA-tr •• ta4 aroup (t'abi. 80 _4
lIlat1ro CO).
Mallc .1lJQ" alao aho-..4 a .s..u.. patteI'D of
1ta eotty!t, atter •• tradlo1 .xpoaUS'. or o .... leotcll1.e4
p .. tlll1, b~.t"tOid 1&84 anlllala aJl4 DIIBA-tl" •• t.4
o.ar1eoto~ •• d-par'1al17 bepatactob1 .. 4 ~a1. (Table 16 and Ptgure 44).
GaP.Dn and mallo en.,. _~ pl.., aD ~
role in .BA'Dl'B pr04uotlon bl the tlaw.. aut all4 bi •
... .,ol.t.. (1910.) bave rGpoJtt.4 thac aD, SAo ..... 1D
08P-DH aotlvltr oocura in t~ ta •• of • 4.ore ••• tD
....... ,. 'UllOa- arowth an4y10- !eI"~ S1Do.oldDS •• 10
o&p..oo aotlyity bave been •• aoola:te4 with l1poa ... ala
ana with a.cretora1 acU"ltJ 1D .. .,.A .DClooJ'la. UPS.' l.o
273
oraana. the .eaulatlob or thl. eftQ .. bJ eMooJ'1Dt1 be.-
al , ... tlone .., paPtlallJ. at le ... t, 1 "810_1"1. tor ohange. la tUllOr p-owtb.
o.arl.ottJ., reaul te4 10 a 4.0N_ lD total DIA
oont_, ill ... p,....'1na 11 ... 1I1.00a,p ... 11101l 10 thd 10
the anl_1. wltb In'ao' 0"""8 (table 71 and Flawe t8'. lD coabln.tloD with mtBA al.a .yarleoto., .... ltd In •
4.er.... 1rl total DBA ooat.eat ot resen ... tlac lL.v. The
.tteot. ar. tCUDCl to 'btl additiv. lrl ftat\lPe ad .nc!ocrln. ablation 1. DOt found to hay • .,. intlwmoe 011 DIIlA ••
aotloa on DUel.to ac14. Table V2 and Flgur. t8 abo.
~t •• tradlol v •• iaeJlt ot tha.. two groap. r •• ul t. ill an aleyated le.el or DliA. 'lh8 .. l' •• ulta ... tn Coed
..... _l1t .It,,} tho •• of Spaa1an1 (1963) who 8Qt10eel an
1M .. _" nuabal'ot lualnal epithelial 04111. In ,,'-I
ot oyaplectoMlsed .at alter e.tra4101 tr ...... '. Ilavlna and ..... 11 (lG?a) &lao r.port~ • att.alato17
.. 'Ion ot the ~D8 OD ,,01.10 ac14 .,.* •• 1.. !he
eft .. ,. ot DMBAand Oyul.oto., .... mtllUtec1 111
reseneratins 11.-r .,t2.r .. tradlol adm1nSat..tlon.
'rota]. (1'...,1." and F1gure 62) anel aolubl. proteiD.
oontent5 (Table 83 and Pipe M) .... '-\10.4 at, •• o.""leo'~. Since •• tra41ol 1 •• eported. to .ahaoc. the Qlltb •• la of pl_ prot.lna ln 11.,.,.. o.UleohllJ~-·
274
whlob l" •• ult. in the nearly total ab •• noe of e.tro,_ in the sJ.te= expeoted to deer .... protein con-c.nt 1ft
resea.ratlng liver. In rmBA -treated ,.e,.n.,.atlng 11 .. .-
alac. 1 t re.ul ted In " ctecr.ue except at V2 bJ' wMD
tM 1Dcr..... 10 tot.J. prote1ft (Table ") appear. to 'be
antagonlatlc ertect ot tile two iP •• ~Dt .• la:a •••• D ... '_
11 .... r.
Eatl"e4!ol a4rdn1stJ"atlon, bO •• YR. oould not
rca.tore the deere a.. in total prot.1ft eoDtet (fable '8
anel Figure &2) wher... .01 uble prot.ln cont_t ...
lnoreuod (Table B4 an(l f'lpre 66). SlIlt.larlJ. l'
aftocbed tho total and aolublo protein oontent)sin DeA-
treated ovarleoto.t:ed-partlal17 bepateoto-'aed ant.al ••
FrOJft all the a'bo". d.t., tbe concluloa 0" be
.. 48 1& that the elwa4101 at tJ)e sly.a dO .. 1em (0.5 llil'ks boAy .elgbt) ".du ••• the .tt .. , of DO.
lnlt1allJ. Ov.rleoto., work. to an oppoalte W.nDAP.
Ibm exogeDOU. e.tradlol wa_ asYeD at,. O'f'ar1 •• ~.
1 t countvaote4 tile aotlOft or DdJ. m4 OY .. leo~.,
011 aU the 8n~_. exoept) 09' .... 011, !.DB and tosa).
protein content or the it.,... !b ••• 1ni'lal clum •••
bl'oup,t about b7 •• "'08- In reseneratlq 11 ... IIIIJ
Q%" .., DOt be related to t'be lnoidenoe of bepa~ ... ol--
275
at latar ataaea. With thtt available data, no ".tlclt. oonclus10n oan b. ade witb regal"4 ot tb ••• 1»10-
ab •• loal cbance. indUoed '" eatroaen and ''UIICW inoidenoe.