Madle E, Korte A, Beek B
Teratog Carcinog Mutagen. 1986;6(1):1-13. doi: 10.1002/tcm.1770060102.
Three animal species used in in vivo mutagenicity testing--rats, mice and Chinese hamsters--were compared with respect to their mutagenic response to the mycotoxin aflatoxin B1 (AFB1). The micronucleus test and the SCE test with bone marrow cells were chosen as test methods, employing similar protocols for all species. The mutagenic potential of AFB1 was detected with rats and mice but not with Chinese hamsters. Rats were more susceptible to the mutagenic action of AFB1 than mice with regard to the effective dose. A difference in sensitivity between males and females was evident in rats and mice: male animals exhibited higher induced micronucleus frequencies than females, and a clear SCE-inducing effect was only detectable in male animals. These results are in agreement with those of in vitro and carcinogenicity studies. They may be due to metabolic differences between the species and sexes, predominantly differences in glutathione conjugation of the reactive AFB1 epoxide and in the formation of the metabolite aflatoxicol. Furthermore, it could be demonstrated that AFB1 seems to be a more potent inducer of micronuclei than of SCE. Since our results obtained with rats and mice were clearly positive, but with the Chinese hamster the mutagenic potential of AFB1 was not detectable with the test systems used, it can be concluded that the choice of an "inappropriate" test species may lead to a false negative judgment on the genotoxic potential of a test compound.
对用于体内诱变性测试的三种动物——大鼠、小鼠和中国仓鼠——就它们对霉菌毒素黄曲霉毒素B1（AFB1）的诱变反应进行了比较。选择骨髓细胞微核试验和姐妹染色单体交换（SCE）试验作为测试方法，对所有物种采用相似的方案。AFB1的诱变潜力在大鼠和小鼠中被检测到，但在中国仓鼠中未被检测到。就有效剂量而言，大鼠比小鼠对AFB1的诱变作用更敏感。在大鼠和小鼠中，雄性和雌性之间的敏感性差异明显：雄性动物诱导的微核频率高于雌性，并且只有在雄性动物中才能检测到明显的SCE诱导效应。这些结果与体外和致癌性研究的结果一致。它们可能是由于物种和性别之间的代谢差异，主要是活性AFB1环氧化物的谷胱甘肽结合以及代谢物黄曲霉毒素醇形成方面的差异。此外，可以证明AFB1似乎是一种比SCE更有效的微核诱导剂。由于我们用大鼠和小鼠获得的结果明显为阳性，但在中国仓鼠中，使用的测试系统未检测到AFB1的诱变潜力，因此可以得出结论，选择“不合适”的测试物种可能会导致对测试化合物的遗传毒性潜力做出错误的阴性判断。
