Cytogenetic effect of dapsone, an antileprotic drug, in the mouse in vivo system

Potential genotoxicity of dapsone was evaluated in mice following in vivo cytogenetic assays. Adult male mice treated with different doses (20 mg, 40 mg, or 80 mg/kg/day for 4 weeks) and for different periods (40 mg/kg/day for 2, 4, or 8 weeks) provided bone marrow and testes for mitotic and meiotic chromosome analyses, respectively. A dose-response (20 mg, 40 mg, or 80 mg/kg/day for 2 weeks) analysis was done with a separate set of mice using a micronucleus test (MNT). Untreated mice served as controls. Both the metaphase analysis and MNT in bone-marrow cells revealed significantly higher incidences of clastogenicity for all of the dose levels and treatment periods. Chromosome aberrations, with and without gaps, in bone-marrow metaphases showed a positive correlation with the doses, but not with the treatment periods. Correlation was also lacking in the MNT. In the meiotic cells, the incidences of chromosome aberrations increased significantly with the highest dose and with the longest period of treatment.