Cytogenetic toxicity of methotrexate in mouse bone marrow

Methotrexate (MTX), a widely used anticancer drug, was tested for its cytogenetic toxicity in mouse bone marrow after a single intraperitoneal treatment with three different doses i.e. at the rate of 2, 10 and 20 mg/kg b.w. of mice. The end points selected were chromosomal aberrations and mitotic index study at 24-h post-treatment and micronucleus (MN) test at 30-h post-treatment. The induction of statistically significant number of chromosomal aberrations, percentage of aberrant metaphases and highly significant number of MN per thousand polychromatic erythrocytes by all the doses of MTX indicated it as highly clastogenic. MTX was found more clastogenic in male mice than the females and the intermediate dose tested (10 mg/kg) was found more effective than the other doses. In mitotic index study, none of the doses of MTX inhibited cell proliferation during the first post-treated cell cycle. The results were compared with the earlier reports on the clastogenicity and cell proliferation inhibition of MTX only after multiple treatments. The possible mechanism of the cytogenetic effects of MTX has been discussed.