Spalding J W, French J E, Stasiewicz S, Furedi-Machacek M, Conner F, Tice R R, Tennant R W
National Institute of Environmental Health Sciences, Laboratory of Environmental Carcinogenesis and Mutagenesis, Research Triangle Park, North Carolina 27709, USA.
Toxicol Sci. 2000 Feb;53(2):213-23. doi: 10.1093/toxsci/53.2.213.
The haplo-insufficient p53 knockout (p53+/-) and zetaglobin v-Ha-ras (Tg.AC) transgenic mouse models were compared to the conventional two rodent species carcinogen bioassay by prospectively testing nine chemicals. Seven of the chemicals classified as carcinogens in the conventional bioassay induced tumors in the liver or kidneys of B6C3F1 mice, and one (pentachlorophenol) also induced tumors in other tissues. Only three chemicals, furfuryl alcohol, pyridine, and pentachlorophenol, induced tumors in rats. The tumorigenic effect of pyridine was seen in F344 rats but not in Wistar strain rats. None of the chemicals induced tumors in the p53+/- transgenic mice, which 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 that these transgenic models do not respond to many chemicals that show strain- or species-specific responses in conventional bioassays.
通过对九种化学物质进行前瞻性测试，将单倍体不足的p53基因敲除（p53+/-）和ζ球蛋白v-Ha-ras（Tg.AC）转基因小鼠模型与传统的两种啮齿动物致癌物生物测定法进行了比较。在传统生物测定中被归类为致癌物的七种化学物质在B6C3F1小鼠的肝脏或肾脏中诱发了肿瘤，其中一种（五氯苯酚）还在其他组织中诱发了肿瘤。只有三种化学物质，即糠醇、吡啶和五氯苯酚，在大鼠中诱发了肿瘤。吡啶的致瘤作用在F344大鼠中可见，但在Wistar品系大鼠中未见。这些化学物质在p53+/-转基因小鼠中均未诱发肿瘤，这与这些化学物质无遗传毒性一致。七种非遗传毒性致癌物中只有两种在Tg.AC模型中呈阳性（月桂酸二乙醇胺和五氯苯酚）。这些结果表明，这些转基因模型对许多在传统生物测定中表现出品系或物种特异性反应的化学物质没有反应。
