Induction of micronuclei in mouse and hamster bone-marrow by chemical carcinogens

Four carcinogens, dimethylnitrosamine (DMN), acetylaminofluorene (AAF), aflatoxin B1 (AFB1), and 3-methylcholanthrene (3-MC) were tested acutely and chronically in the micronucleus test in both mice and hamsters. In acute studies using mice, all compounds increased the relative frequency of micronuclei when compared to controls. There was a dose response which tended to tail off as bone-marrow suppression was observed. The order of activity appears to be DMN greater than AFB1 greater than or equal to 3-MC greater than AAF. In acute hamster studies, AFB1 was inactive at the highest dose tested (3 mg/kg). In the case of hamsters, all other compounds increased the incidence of micronuclei with DMN greater than 3-MC greater than AAF. Subacute studies with hamsters revealed that 3-MC was active at 1 week but not 8 weeks while DMN was active at both 1 and 8 weeks. AAF was active at 8 and 12 weeks and AFB1 was active at 12 weeks but not 8 weeks. The authors conclude that this test does not appear useful in chronic protocols and probably more reflects carcinogenicity of the test compounds than acute toxicity. Nevertheless, acute studies demonstrate that this test procedure is of value in the characterization of a compound's relative mutagenic potential.