The evaluation of sixteen carcinogens in the rat using the micronucleus test

Sixteen carcinogens were evaluated in rats for their ability to induce micronuclei. The direct acting agent, ethyl methanesulfonate and the procarcinogens/promutagens, cyclophosphamide and 4-nitroquinoline-1-oxide, induced dose-related increases in micronucleated polychromatophilic erythrocytes. Aflatoxin B1 also significantly increased the number of micronucleated polychromatophillic erythrocytes for 2 doses although no dose-response could be detected. Dimethylnitrosamine produced variable results. The remaining 11 compounds, 2-acetylaminofluorene, 4-aminobiphenyl, benzidine, diethylnitrosamine, dimethylbenzanthracene, 1,2-dimethylhydrazine, ethionine, ethyl carbamate, hexametapol, metronidazole, and beta-naphthylamine, failed to induce significantly increased numbers of micronuclei. The large number of false negative results obtained in the present investigations using the micronucleus test suggests that in vivo cytogenetic assays utilizing bone marrow may also lack the sensitivity needed to detect clastogenic effects of procarcinogens/promutagens which require tissue specific metabolic activation.