Responses of transgenic mouse lines p53(+/-) and Tg center dot AC to agents tested in conventional carcinogenicity bioassays

The haplo-insufficient p53 knockout (p53(+/-)) and zetaglobin v-Ha-ras (Tg. AC) transgenic mouse models were compared to the conventional two rodent sp ecies carcinogen bioassay by prospectively testing nine chemicals. Seven of the chemicals classified as carcinogens in the conventional bioassay induc ed tumors in the liver or kidneys of B6C3F(1) mice, and one (pentachlorophe nol) also induced tumors in other tissues. Only three chemicals, furfuryl a lcohol, pyridine, and pentachlorophenol, induced tumors in rats. The tumori genic effect of pyridine was seen in F344 rats but not in Wistar strain rat s. None of the chemicals induced tumors in the p53(+/-) transgenic mice, wh ich is consistent with the absence of genotoxicity of these chemicals. Only two of the seven nongenotoxic carcinogens were positive in the Tg.AC model (lauric acid diethanolamine and pentachlorophenol). These results show tha t these transgenic models do not respond to many chemicals that show strain - or species-specific responses in conventional bioassays.