Mutation Research 349 ( 1996) 289-290

Fundamental and Molecular Mechanisms of Mutagenesis

ELSEVIER

Series: Current Issues in Mutagenesis and Carcinogenesis, No. 66

Lijinsky ‘s observation that the spontaneous tumour incidence in F334 rats is unaffected by prior damage to DNA

John Ashby *

Zrnrcn Central Tmicology Luhomtoty. Alderlry Park, Mucclrsjield. SKI0 4TJ. UK

Received 26 September 1995; accepted 28 September 1995

3,000

2.500 r, Q F344 Rats

2,000

No. of rats necqsied per interval

500

I

80 100 120 140 Interval (wk)

A A A A A A A

dF344 Rats

60 80 100 120 140 Interval (wk)

I A A A A A I

Fig. I. Summary of the literature review conducted by Lijinsky et al. (1993). Spontaneous tumour incidences were recorded for over 10000

F344 rats, groups of which were exposed to either vehicle or one of a total of 148 different alkylating agent carcinogens. The incidence of

turnours at the sites of spontaneous carcinogenesis were then compared between the test and control groups, for each sacrifice interval, as

indicated by the arrows. The spontaneous tumours analysed were: MNL, mononuclear cell leukaemia: AG, pheochromocytomas of adrenal

gland: PT. pituitary tumours; TG. c-cell thyroid gland tumours: P, pancreatic islet cell tumours; T, interstitial cell testicular turnours: MC.

mammary gland fibroadenomas.

* Tel.: 44 1625 582711: Fax: 44 1625 590 249.

0027-5107/96/$15.00 0 1996 El sevier Science B.V. All rights reserved

SSDI 0027-5107(95)00190-5

290 J. Ashby/Mtttution Research 349 (IYY6I 289-290

In 1993, Lijinsky reported the results of an exten-

sive literature review in which the tumour sites and

incidences among groups of control F344 rats were compared to those observed in groups of rats ex-

posed to one or other of 148 different alkylating agents (Lijinsky et al., 1993). The control animals

developed a range of spontaneous tumours at the seven expected sites (see Fig. 1). The alkylating

agents produced tumours in a broad range of addi- tional tissues. Lijinsky then analysed the combined

data and found that the incidence of tumours at the

seven sites of spontaneous carcinogenesis was gener-

ally the same, or lower, among the chemically treated

animals than that seen in the concurrently necropsied

vehicle control animals. Lijinsky concluded that the aetiology of the spontaneous tumours was different

to that of the chemically induced tumours. in particu- lar, that the process of spontaneous carcinogenesis in

F344 rats is not enhanced by prior treatment of the animals with DNA damaging agents. This finding,

based on the observation of over 10000 rats, con-

tributes to the legitimacy of the separate considera-

tion of genotoxic and non-genotoxic mechanisms of chemically induced cancer in rodents (cf. also, Fer- reiria-Gonzales et al., 1995). It is therefore curious

that in the subsequent 2 years, only two citations (both made by Lijinsky) to this paper are revealed by

a Science Citation review of the literature. It is hoped that Fig. 1 presented here, which

summarises the complex study undertaken by Lijin-

sky, will focus attention onto what appears to be a

seminal observation made by him.

References

Ferreiria-Gonzales A.. A.B. DeAngelo, S. Nasim and C.T. Garrett

( 1995), Rat oncogene activation during hepatocarcinogenesis

in B6C3Fl male mice by dichloroacetic and trichloroacetic

acid, Carcinogenesis. 16. 495-501.

Lijinsky, W.. C.W. Riggs and P.T. Walters (1993) Lack of effect

of carcinogen treatment on development of tumours arising

spontaneously in Fischer 344 rats. J. Toxicol. Environ. Health,

39. 527-538.