A brief history of the use of laboratory animals for the prediction of carcinogenic risk for man with a note on needs for the future.

This review discusses developments during the last 60 years in the field of carcinogenicity testing based on the use of laboratory animals. Improvements that have occurred in the quality of animals and in the way in which tests are conducted are considered, along with the importance of distinguishing between fatal and incidental tumours. Still to be faced is a need to control calorie intake in the course of carcinogenicity testing. A necessity for a better understanding of how disturbances of physiological and/or hormonal status can predispose to tumour development and for more comparative metabolism studies is stressed. Recognition of the fact that thresholds exist for carcinogenesis by non-genotoxic compounds poses a need for avoiding unrealistically high levels of exposure and for more and better information on how different species metabolise test agents.

[1]  P. Shubik,et al.  A New, Quantitative, Approach to the Study of the Stages of Chemical Carcinogenesis in the Mouse's Skin , 1947, British Journal of Cancer.

[2]  B. Ames Mutagenesis and carcinogenesis: Endogenous and exogenous factors , 1989, Environmental and molecular mutagenesis.

[3]  P. Rous,et al.  THE INITIATING AND PROMOTING ELEMENTS IN TUMOR PRODUCTION , 1944, The Journal of experimental medicine.

[4]  L. Fishbein Biological Effects of Dietary Restriction , 2012, ILSI Monographs.

[5]  Katsusaburo Yamagiwa,et al.  Experimental Study of the Pathogenesis of Carcinoma , 1918 .

[6]  P. Rous,et al.  CONDITIONAL NEOPLASMS AND SUBTHRESHOLD NEOPLASTIC STATES , 1941, The Journal of experimental medicine.

[7]  P. Lee,et al.  The Biosure Study: influence of composition of diet and food consumption on longevity, degenerative diseases and neoplasia in Wistar rats studied for up to 30 months post weaning. , 1995, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[8]  B. Ames,et al.  Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. , 1983, Science.

[9]  B. S. Oppenheimer,et al.  Sarcomas Induced in Rats by Implanting Cellophane , 1948, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[10]  N. M. Kennaway,et al.  The production of cancer by pure hydrocarbons. V , 1932, Proceedings of the Royal Society of London. Series B - Biological Sciences.

[11]  I. Berenblum,et al.  An Experimental Study of the Initiating Stage of Carcinogenesis, and a Re-examination of the Somatic Cell Mutation Theory of Cancer , 1949, British Journal of Cancer.

[12]  I. Berenblum,et al.  The Role of Croton Oil Applications, Associated with a Single Painting of a Carcinogen, in Tumour Induction of the Mouse's Skin , 1947, British Journal of Cancer.

[13]  I. Berenblum,et al.  The Persistence of Latent Tumour Cells Induced in the Mouse's Skin by a Single Application of 9:10-Dimethyl-1:2-Benzanthracene , 1949, British Journal of Cancer.

[14]  B. Ames,et al.  Thymine glycol and thymidine glycol in human and rat urine: a possible assay for oxidative DNA damage. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[15]  B. Ames,et al.  Too many rodent carcinogens: mitogenesis increases mutagenesis. , 1990, Science.

[16]  R Peto,et al.  Editorial: Guidelines on the analysis of tumour rates and death rates in experimental animals. , 1974, British Journal of Cancer.

[17]  J Wahrendorf,et al.  Guidelines for simple, sensitive significance tests for carcinogenic effects in long-term animal experiments. , 1980, IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Supplement.

[18]  F. Roe,et al.  Enzootic and Epizootic Adrenal Medullary Proliferative Disease of Rats: Influence of Dietary Factors which Affect Calcium Absorption , 1985, Human toxicology.

[19]  A. Tannenbaum The Genesis and Growth of Tumors. II. Effects of Caloric Restriction per se , 1942 .

[20]  E. Nera,et al.  Calorie restriction and cellular proliferation in various tissues of the female Swiss Webster mouse. , 1990, Cancer letters.

[21]  J. Miller,et al.  A mechanism of orthol-hydroxylation of aromatic amines in vivo. , 1960, Biochimica et biophysica acta.

[22]  W. Gardner Hormonal imbalances in tumorigenesis. , 1948, Cancer research.

[23]  M. Tucker The effect of long‐term food restriction on tumours in rodents , 1979, International journal of cancer.

[24]  M. Surks,et al.  Increased thyroxine turnover and thyroidal function after stimulation of hepatocellular binding of thyroxine by phenobarbital. , 1968, The Journal of clinical investigation.

[25]  M. Biskind,et al.  Development of Tumors in the Rat Ovary After Transplantation into the Spleen. , 1944 .

[26]  Richard Weindruch,et al.  The Retardation of Aging and Disease by Dietary Restriction , 1988 .