Study on Rapid Carcinogenicity Test Using Transgenic Mice

在本研究中，我们研究了携带人类原型c-Ha-ras基因的转基因小鼠Tg rasH2/CB6F1小鼠对各种遗传毒性致癌基因的致癌反应，并将其与对照非转基因CB6F1小鼠（非Tg小鼠）进行了比较。本研究是作为快速致癌性检测系统的模型进行的。4-硝基喹啉-1-氧化物、环磷酰胺、N，N-二乙基亚硝胺、N-甲基-N-亚硝基脲、N-甲基-N'-硝基-N-亚硝基胍和甲基氧基甲醇等多种遗传毒性致癌物的短期（*6个月）快速致癌性试验显示，Tg rasH2/CB6F1小鼠比对照非Tg小鼠对这些遗传毒性致癌物更敏感。Tg rasH2/CB6F1小鼠与非Tg小鼠相比，肿瘤发展更快。恶性肿瘤仅在经致癌物处理的Tg rasH2/CB6F1小鼠中观察到，而在经相同致癌物处理的非Tg小鼠中没有观察到。每种致癌物在相应靶点诱导的tg rasH2/CB6F1小鼠肿瘤发生。在几个月的癌变试验中，只有极少数肺腺瘤而没有其他肿瘤被视为自发性肿瘤。这些结果表明，Tg rasH2-/CB6F1小鼠在接受各种遗传毒性致癌物治疗后，比对照非Tg小鼠发作更快，恶性肿瘤发生率更高。Tg rasH2/CB6F1小鼠似乎是开发快速致癌性测试系统的有希望的候选动物模型。

In this study, we investigated the carcinognic response of transgenic mice carrying the human prototype c-Ha-ras gene, namely Tg rasH2/CB6F1 mice, to various genotoxic carcinogenes and compared it with that of control non-transgenic CB6F1 mice (non-Tg mice). The present studies were conducted as a model for the rapid carcinogenicity testing system. Short-term (*6 months) rapid carcinogenicity tests of various genotoxic carcinogens, 4-nitroquinoline-1-oxide, cyclophosphamide, N,N-diethyl-nitrosamine, N-methyl-N-nitrosourea, N-metyl-N'-nitro-N-nitrosoguanidine and methylazoxymethanol, revealed that Tg rasH2/CB6F1 mice are more susceptible to these genotoxic carcinogens than control non-Tg mice. Tg rasH2/CB6F1 mice developed tumors more rapidly compared with non-Tg mice. Malignant tumors were observed only in the carcinogen-treated Tg rasH2/CB6F1 mice, but not in non-Tg mice treated with the same carcinogens. Each carcinogen induced tumors in corresponding target of the tg rasH2/CB6F1 mice. Only a very few lung adenomas but no other tumors were seen as spontaneous tumors during the months of carcnogenicity tests. These results demonstrate that more rapid onset and higher incidence of more malignant tumors can be expected with high probability after treame with various genotoxic carcinogens in the Tg rasH2-/CB6F1 mice than in control non-Tg mice. The Tg rasH2/CB6F1 mouse seems to be a promising candidate as an animal model for the development of a rapid carcinogenicity testing system.