McGregor D B
International Agency for Research on Cancer, Lyon, France.
IARC Sci Publ. 1992(116):323-52.
Chemicals classified by the IARC to its groups 1, 2A, 2B and 3 were examined in an attempt to identify characteristics of their behaviour in experimental studies of carcinogenicity, genotoxicity and acute mammalian toxicity that correlate with those categories. Only those agents for which information on carcinogenic potency was available were studied. In both mice and rats, more chemicals were potent carcinogens if they had been categorized in Group 1 (human carcinogens) than if they had been put into one of the other categories. Not surprisingly, there was a weak association between carcinogenic potency and acute toxicity. Mice were especially sensitive to tumour induction by halides; the lower sensitivity of rats to any carcinogenic effect of halides could be due in part to their higher systemic toxicity in this species: a reduced differential of toxic and carcinogenic doses decreases the dose window in which carcinogenic effects may be demonstrated. It was notable that the human carcinogens were active in those genotoxicity tests with higher specificity for identifying rodent carcinogens. Predictive assays for carcinogenicity that were considered to be highly specific were tests for cytogenetic effects in vivo, unscheduled DNA synthesis in hepatocytes, mutation in any of the five commonly used strains of Salmonella typhimurium and mutation at the hprt locus in mammalian cells. None of the relationships was strong enough to form the basis of a simple categorization, but they could serve to alert investigators to chemicals of special toxicological interest and importance.
对国际癌症研究机构(IARC)归类为1类、2A类、2B类和3类的化学物质进行了研究,旨在确定它们在致癌性、遗传毒性和急性哺乳动物毒性实验研究中的行为特征,这些特征与上述类别相关。仅研究了那些具备致癌效力信息的物质。在小鼠和大鼠中,被归类为1类(人类致癌物)的化学物质中,强效致癌物的数量多于被归入其他类别的化学物质。不出所料,致癌效力与急性毒性之间存在微弱关联。小鼠对卤化物诱导肿瘤尤为敏感;大鼠对卤化物致癌作用的敏感性较低,部分原因可能是卤化物在该物种中的全身毒性较高:毒性剂量和致癌剂量之间差异的减小会降低能够显示致癌作用的剂量范围。值得注意的是,人类致癌物在那些对鉴定啮齿动物致癌物具有较高特异性的遗传毒性试验中表现出活性。被认为具有高度特异性的致癌性预测试验包括体内细胞遗传学效应试验、肝细胞中非程序性DNA合成试验、五种常用鼠伤寒沙门氏菌菌株中任何一种的突变试验以及哺乳动物细胞中hprt基因座的突变试验。这些关系均不够强,不足以构成简单分类的基础,但它们可用于提醒研究人员关注具有特殊毒理学意义和重要性的化学物质。