Blunt Cell Growth Potential in Carcinogen Resistant Inbred DRH Rats.

Abstract

A carcinogen-resistant inbred strain DRH/Sea has been developed from the Crj:Donryu strain. The rats had a very low incidence of liver tumors when they were fed diets containing a hepatocarcinogen such as 3'-methyl-4-dimethylamino-azobenzene (3'-Me-DAB). Despite using 3'-Me-DAB during the stage of selection, the DRH/Sea rats developed normally, reproduced and did not have any spontaneous tumor in the lung, liver or uterus at over 1 year of age. Although their growth curves were similar to the Crj:Donryu rats, the progression of polyploidization in the liver was significantly delayed when compared with Crj:Donryu rats. Mitogenic changes that occurred in the liver caused by either 3'-Me-DAB or lead nitrate were less significant in the DRH rats than in Crj:Donryu rats. Furthermore, the growth rate of cultured fibroblasts derived from the DRH rats was slower than that of Crj:Donryu rats. These results, together with our previous results, suggest that slow growth potential is present under certain conditions in DRH rats. These findings may explain partly the meaning of the different susceptibility to hepatocarcinogens. Key words: carcinogen-resistant rat, DRH/Sea, growth potential, ploidy but also in the uterus and via the milk. A pair of 12-week-old rats from the same litter were inbred and the rests were employed occasionally for the examination of either GGT-induction or hepatocarcinogenesis caused by 3'-Me-DAB. Therefore, many groups for inbreeding were maintained simultaneously, that is, more than 40 family lines on occasions. During this process, litters of rats that were premature at birth or grew poorly (Received 5 April 1999 / Accepted 8 July 1999 Corresponding address: K. Higashi, Department of Biochemistry, School of Medicine, University of Occupational and Environmental Health, Yahatanishiku, Japan Carcinogen-resistant rats were first isolated from Crj:Donryu rats (Charles River Japan, Inc.) based on examination of selective markers such as reduced induction of γ-glutamyltranspeptidase (GGT) and a very low incidence of liver tumors due to 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) [10,11]. Briefly, all the rats were exposed continuously to 3'-Me-DAB and its metabolites not only after weaning