Anticlastogenic effects of centchroman and its enantiomers in Swiss albino mice. I. Acute study and their comparison with tamoxifen

Abstract

Centchroman (CC), a non steroidal oral contraceptive and a candidate drug for breast cancer, has been reported to exhibit partial to complete remission of lesions in 40.5% of breast cancer patients. Recently, we have reported the antimutagenic effects of CC in multiple mutational assays. The potent antioestrogenic activity, negligible side effects, anti-breast cancer activity and antimutagenic effects of CC prompted us to evaluate the anticlastogenic effects of CC and two of its enantiomers. i.e. d-centchroman (DC) and l-centchroman (LC) in the acute in vivo studies in female Swiss albino mice as measured by chromosome aberrations (CA) and sister chromatid exchange (SCE) assays against two known positive mutagen compounds, i.e. dimethylbenz[ a]anthracene (DMBA) and cyclophosphamide (CP). The results of anti-mutagenicity assays of CC and its enantiomers have been compared to the known breast cancer drug tamoxifen (TM). CC and LC reduced both DMBA and CP induced CA when compared with the group treated with only DMBA and CP. DC did not reduce the DMBA-induced CA when compared with the DMBA-treated group alone. It reduces only the CP induced CA. TM also reduces both DMBA and CP induced CA when compared with group received only DMBA or CP. SCE were carried out only for LC. A weak but significant decrease in SCE was observed in both LC plus DMBA- and LC plus CP-treated groups when compared with respective positive controls alone. Thus the overall results indicate that both CC and LC are more effective in reducing the genotoxic effects of DMBA and CP than DC.