Pai

ntin

g an

alys

is o

f chr

omos

ome

aber

ratio

ns in

duce

d by

ene

rget

ic h

eavy

ions

in h

uman

cel

ls

Hon

glu

Wu,

Meg

umi H

ada

and

Fran

cis

Cuc

inot

taN

AS

A J

ohns

on S

pace

Cen

ter

https://ntrs.nasa.gov/search.jsp?R=20070021453 2020-03-03T08:37:13+00:00Z

S

GA

LAC

TIC

CO

SM

IC R

AD

IATI

ON

(GC

R)

(Pro

tons

to Ir

on N

ucle

i)

SO

UTH

ATL

AN

TIC

AN

OM

ALY

(Pro

tons

)

INN

ER

RA

DIA

TIO

N B

ELT

(Pro

tons

)

OU

TER

RA

DIA

TIO

N B

ELT

(Ele

ctro

ns)Th

e S

pace

Rad

iatio

nE

nviro

nmen

t

SO

LAR

PA

RTI

CLE

EV

EN

T(P

roto

ns to

Iron

Nuc

lei)

Rep

rese

ntat

ion

of th

e m

ajor

sou

rces

of i

oniz

ing

radi

atio

n of

impo

rtanc

eto

man

ned

mis

sion

s in

low

-Ear

th o

rbit.

Not

e th

e sp

atia

l dis

tribu

tion

ofth

e tra

pped

radi

atio

n be

lts.

NO

UTE

R R

AD

IATI

ON

BE

LT(E

lect

rons

)

Gal

acti

c co

smic

rad

iati

on

DS

B in

duct

ion

Low

-LE

TH

igh-

LET

http://www.nih.gov/sigs/dna-rep/

Com

plex

abe

rrat

ions

Wu,

Dur

ante

, Geo

rge

and

Yan

g, R

adia

t. R

es.(

1997

)

Rad

iatio

n-in

duce

d ch

rom

osom

e ab

erra

tions

in ly

mph

ocyt

es in

vitr

o

Ana

lysi

s of

trul

y in

com

plet

e ex

chan

ges

usin

g te

lolm

ere

prob

es

Telo

mer

e A

naly

sis

Wu,

Geo

rge

and

Yan

g, IJ

RB

(199

8, 1

999)

Mos

t of t

he in

com

plet

e ex

chan

ges

anal

yzed

with

FI

SH

are

act

ually

com

plet

e

0

0.1

0.2

0.3

0.4

0.1

110

100

1000

Unr

ejoi

ned/

Mis

rejo

ined

Inco

mpl

ete/

Com

plet

e

LET

(keV

/mic

ron)

Wu,

Dur

ante

, Fur

usaw

a, G

eorg

e, K

awat

aan

d C

ucin

otta

, Rad

. Res

. (20

03)

0

0.02

0.04

0.06

0.080.

1 0.1

110

100

1000

LET

(ke

V/m

icro

n)

Gam

ma

490

MeV

/uSi

500

MeV

/uFe

200

MeV

/u F

e

•The

frac

tion

of u

nrej

oine

d ch

rom

osom

e br

eaks

are

hig

her f

or h

igh

LET

•Unr

ejoi

ned

brea

ks a

nd in

com

plet

e ch

rom

osom

al e

xcha

nges

are

pos

sibl

e bi

osig

natu

res

of h

igh-

LET

radi

atio

n

Hig

h-LE

T ra

diat

ion

indu

ces

mor

e un

rejo

ined

DN

A d

oubl

e st

rand

bre

aks

Des

ai, D

avis

, O’N

eill,

Dur

ante

, Cuc

inot

taan

d W

u, R

ad. R

es. 2

005

Si

Fe

Com

plex

abe

rrat

ions

--m

FIS

Han

alys

is

Sim

ple

exch

ange

Com

plex

ex

chan

ge

Wu,

Dur

ante

, Fur

usaw

a, G

eorg

e, K

awat

aan

d C

ucin

otta

, Adv

. Spa

ce R

es. (

2002

)

BIO

SIG

NA

TUR

E O

F H

IGH

-LE

T R

AD

IATI

ON

0

0.050.1

0.150.2

0.250.3

Com

plex

/sim

ple

exch

ange

sIn

com

plet

e/co

mpl

ete

exch

ange

s

Ratio

Gam

ma

6 G

y

Fe io

ns 3

Gy

Fe io

ns 0

.7 G

ym

FIS

Hsh

owed

a h

ighe

r fra

ctio

n of

com

plex

and

in

com

plet

e ex

chan

ges

for

high

-LE

T

0

0.2

0.4

0.6

0.81

1.2

1.4

1.6

1.8

Gam

ma

6 G

yFe

ions

3 G

yFe

ions

0.7

Gy

2-w

ay e

xcha

nge

3-w

ay e

xcha

nge

4-w

ay e

xcha

nge

5-w

ay e

xcha

nge

6-w

ay e

xcha

nge

7-w

ay e

xcha

nge

8-w

ay e

xcha

nge

Com

plex

type

abe

rrat

ions

0

0.050.1

0.150.2

0.250.3

0.35

01

23

45

67

(b)

5 G

y ga

mm

aM

etap

hase

PC

C

Num

ber

of a

ber

rati

ons

Wu,

Geo

rge,

Kaw

ata,

Willi

ngha

m a

nd C

ucin

otta

, Rad

. Res

. 200

1

Inte

rpha

se v

s. m

etap

hase

: Iss

ues

of b

iosi

gnat

ure

Rad

iatio

nD

ose

(Gy)

Har

vest

m

etho

dF

ratio

γ ra

y2

PC

C15

.3±6

.3

γ ra

y2

Met

a12

.5±5

.9

γ ra

y5

PC

C8.

2±2.

0

γ ra

y5

Met

a9.

1±2.

5

1 G

eV/u

Fe3

PC

C5.

2±0.

9

1 G

eV/u

Fe3

Met

a9.

1±2.

2

Cen

trom

ere

prob

es w

ere

used

.

mB

AN

Dan

alys

is

Inte

r-vs

. int

ra c

hrom

osom

e ex

chan

ges

(mB

AN

D)

0

0.1

0.2

0.3

0.4

0.5

01

23

4

Intra

-exc

hang

eIn

ter-

exch

ange

01

23

4

137

Cs

γ-ra

y F

e (6

00 M

eV/n

)

Dos

e (G

y)

Aberrations in chromosome 3 / cell

Dos

e (G

y)

Fraction in damaged chromosome 3

0

0.2

0.4

0.6

Com

plex

exc

hang

eS

impl

e ex

chan

ge

2

4

0.2

5

0.5

1.0

1.5

2

.0

137C

s γ-

ray

Fe (6

00 M

eV/n

)

Fraction of total inversion

0

0.2

0.4

0.6

0.8

Inv+

Intra

+Int

erIn

v+In

ter

Inv+

Intra

Inv

137C

s γ-

rays

Fe

(600

MeV

/n)

mB

AN

Dan

alys

is

Mos

t inv

ersi

ons

wer

e in

volv

ed

with

oth

er in

ter-

and/

or in

tra-

chro

mos

ome

rear

rang

emen

ts

Sum

mar

y

•FI

SH

, mFI

SH

, mB

AN

D, t

elom

ere

and

cent

rom

ere

prob

es h

ave

been

use

d to

stu

dy c

hrom

osom

e ab

erra

tions

indu

ced

in h

uman

ce

lls e

xpos

ed to

low

-and

hig

h-LE

T ra

diat

ion

in v

itro

•H

igh-

LET

indu

ced

dam

ages

are

mos

tly a

sin

gle

track

effe

ct

•U

nrej

oine

d ch

rom

osom

e br

eaks

(inc

ompl

ete

exch

ange

s) a

nd

com

plex

type

abe

rrat

ions

wer

e hi

gher

for h

igh-

LET

•B

iosi

gnat

ures

may

dep

end

on th

e m

etho

d th

e sa

mpl

es a

re

colle

cted

•R

ecen

t mB

AN

Dan

alys

is h

as re

veal

ed m

ore

info

rmat

ion

abou

t the

na

ture

of i

ntra

-chr

omos

ome

exch

ange

s

Meg

umi H

ada

Fran

k C

ucin

otta

Dip

taB

andy

opad

hyay

Nira

vD

esai

Mar

co D

uran

teY

oshi

yaFu

rusa

wa

Ker

ry G

eorg

eTe

tsuy

a K

awat

aV

eron

ica

Will

ingh

am