Sex difference in the micronucleus test

Abstract

Since sex difference seemed to be one of the most urgent issues to be clarified among many parameters in protocols for the micronucleus test, the collaborative study group for the micronucleus test, consisting of members of the Japanese Environmental Mutagen Society, focused on this subject first. 20 clastogens were examined for sex-related differences of response in the micronucleus test with male and female mice at 20 participating laboratories, one at each laboratory. The results obtained were analyzed and 10 out of the 20 compounds were chosen for further tests for confirmation and re-examination. As a rule, each retested compound was evaluated at 2 laboratories with different strains of mice. The overall results of the first and second trials indicate that (1) all compounds induced micronuclei in both male and female mice, (2) 2-acetylaminofluorene (2-AAF), benzene, benzo[ a]pyrene (B[ a]P), and 7,12-dimethylbenzanthracene (DMBA) induced significantly higher incidences of micronuclei in males than in females, (3) ethyl methanesulfonate induced more micronuclei in females than in males, and (4) the other compounds showed almost the same responses in males and females or slightly higher responses in males than in females. The higher susceptibility of male mice to 2-AAF, B[ a]P, and DMBA has, to our knowledge, not previously been reported. Based upon these results, we suggest that the use of male mice is sufficient for general screening by the micronucleus test.