Cytogenetic toxicity of methotrexate in mouse bone marrow

Methotrexrate (MTX), a widely used anticancer drug, was tested for its cyto genetic toxicity in mouse bone marrow after a single intraperitoneal treatm ent 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 i ndex study at 24-h post-treatment and micronucleus (MN) test at 30-h post-t reatment. The induction of statistically significant number of chromosomal aberrations, percentage of aberrant metaphases and highly significant numbe r of MN per thousand polychromatic erythrocytes by all the doses of MTX ind icated it as highly clastogenic. MTX was found more clastogenic in male mic e than the females and the intermediate dose tested (10 mg/kg) was found mo re effective than the other doses. In mitotic index study, none of the dose s of MTX inhibited cell proliferation during the first post-treated cell cy cle. The results were compared with the earlier reports on the clastogenici ty and cell proliferation inhibition of MTX only after multiple treatments. The possible mechanism of the cytogenetic effects of MTX has been discusse d. (C) 2000 Elsevier Science B.V. All lights reserved.