Micronucleus test in rats after oral administration of methyl methanesulfonate for 4 weeks

概要

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As a part of an extensive collaborative study of micronucleus assays, we examined whether the micronucleus test can be integrated into the 4-week general toxicity study of rats in a study in which methyl methanesulfonate (MMS) was administered at doses of 3, 10, and 30 mg/kg/day. The results can be summarized as follows : 1) Increased frequencies of reticulocytes with micronucleus in peripheral blood was observed from the second day of administration in the 10 and 30 mg/kg/day groups. 2) Increased frequencies of immature erythrocytes with micronucleus of bone marrow was observed in the 30 mg/kg group. 3) There were no effects on the incidence of mature erythrocytes with micronucleus in either peripheral blood or bone marrow in any dose group. 4) On histopathological examination, an inhibitory effect of MMS on development of sperm but no effect in the spleen was observed. These results obtained with MMS suggest that it is possible to integrate the micronucleus assay into general toxicity studies using rats. The peripheral blood samples collected at the 3rd day after the beginning of treatment and bone marrow and peripheral blood samples collected at necropsy 4 weeks after the beginning of treatment were shown to be reliable for assessment of the frequency of micronucleated cells.
日本環境変異原学会の論文
2000-12-22