RAPID INDUCTION OF MORE MALIGNANT-TUMORS BY VARIOUS GENOTOXIC CARCINOGENS IN TRANSGENIC MICE HARBORING A HUMAN PROTOTYPE C-HA-RAS GENE THANIN CONTROL NONTRANSGENIC MICE
S. Yamamoto et al., RAPID INDUCTION OF MORE MALIGNANT-TUMORS BY VARIOUS GENOTOXIC CARCINOGENS IN TRANSGENIC MICE HARBORING A HUMAN PROTOTYPE C-HA-RAS GENE THANIN CONTROL NONTRANSGENIC MICE, Carcinogenesis, 17(11), 1996, pp. 2455-2461
In this study, we investigated the carcinogenic response of transgenic
mice carrying the human prototype c-aa-ras gene, namely Tg rasH2/CB6F
1 mice, to various genotoxic carcinogens and compared it with that of
control nontransgenic CB6F1 mice (non-Tg mice), The present studies we
re conducted as the first step in the evaluation of the Tg rasH2/CB6F1
mouse as a model for the rapid carcinogenicity testing system. Short-
term (less than or equal to 6 months) rapid carcinogenicity tests of v
arious genotoxic carcinogens, 4-nitroquinoline-1-oxide, cyclophosphami
de, N,N-diethylnitrosamine, N-methyl-N-nitrosourea, N-methyl-N'-nitro-
N-nitrosoguanidine and methylazoxymethanol, revealed that Tg rasH2/CB6
F1 mice are more susceptible to these genotoxic carcinogens than contr
ol non-Tg mice. Tg rasH2/CB6F1 mice developed tumors more rapidly comp
ared with non-Tg mice, Malignant tumors were observed only in the carc
inogen-treated Tg rasH2/CB6F1 mice, but not in non-Tg mice treated wit
h the same carcinogens, Each carcinogen induced tumors in correspondin
g target tissues of the Tg rasH2/CB6F1 mice, Only a very few lung aden
omas but no other tumors were seen as spontaneous tumors during the 6
months of carcinogenicity tests, These results demonstrate that more r
apid onset and higher incidence of more malignant tumors can be expect
ed with high probability after treatment with various genotoxic carcin
ogens in the Tg rasH2/CB6F1 mice than in control non-Tg mice. The Tg r
asH2/CB6F1 mouse seems to be a promising candidate as an animal model
for the development of a rapid carcinogenicity testing system.