Species differences in mutagenicity testing: I. Micronucleus and SCE tests in rats, mice, and Chinese hamsters with aflatoxin B1.
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.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects* / Q000648:ultrastructure; D002869:Chromosome Aberrations; D006224:Cricetinae; D003520:Cyclophosphamide / Q000633:toxicity; D005260:Female; D008297:Male; D051379:Mice; D008940:Mitotic Index / Q000187:drug effects; D009152:Mutagenicity Tests / Q000379:methods*; D051381:Rats; D012737:Sex Factors; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013045:Species Specificity
D000348:Aflatoxins; D003520:Cyclophosphamide; D016604:Aflatoxin B1