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The tissue culture condition that is required for the type of chromosome breakage seen at most fragile sites, namely, the absence of folic acid and thymidine in the medium, greatly enhanced micronucleus formation in proliferating lymphocyte cultures from normal individuals. This suggests that chromosome breakage at fragile sites and the apparently spontaneous damage that gives rise to micronuclei are controlled by the same mechanism.

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.

Comparative investigations of sister-chromatid exchange (SCE) and micronucleus induction in the bone marrow of rats, mice and Chinese hamsters with the cytostatic alkylating mutagen cyclophosphamide (CP) revealed remarkable species differences in their mutagenic responses. With both test systems the sensitivities of the three species can be ranked into the order rat greater than mouse greater than Chinese hamster. More explicit results were obtained with the SCE test than with the micronucleus test within the same dose range. This may be due to the influence of species-related differences in the cytotoxic response to CP in the micronucleus test. These results show that clearly different mutagenic responses in different test species may be obtained in standard assays even with a compound which is metabolized in a very similar manner in all animal species.