Comparative antimutagenic effects of D- and L-centchroman and their comparison with tamoxifen in Salmonella assay.
Centchroman (CC)--a contraceptive and a candidate drug for breast cancer has been developed by the Central Drug Research Institute. It has been successfully marketed as a contraceptive for last several years. CC has also been reported to exhibit partial to complete remission of lesions in 40.5% breast cancer patients. Recently, we have reported the antimutagenic effects of CC in Ames Salmonella assay and in vivo and in vitro mammalian cells in multiple mutational assay. The potent antimutagenic activity of CC and its anti-breast cancer activity prompted us to evaluate the antimutagenic effects of its enantiomers, i.e., D-centchroman (DC) and L-centchroman (LC) in the Ames Salmonella strains TA97a, TA98, TA100 and TA102 against known bacterial mutagens. Attempts have also been made to compare the results of antimutagenicity assays of CC and its enantiomers with the known breast cancer drug tamoxifen (TM). The main objective was to identify the best suitable form of CC having antimutagenic effects with anticancer profile similar to TM, would replace the latter for toxicity reasons. When mutagenicity assays were carried out with these compounds as expected like CC, none of these enantiomers or TM showed any mutagenic effects in these Salmonella strains. In the antimutagenicity assay a significantly reduced number of bacterial histidine revertant colonies were observed when positive compounds were co-incubated with certain concentrations of LC compared with bacterial plates treated with respective positive compound. This was observed in some concentrations in all the four strains in both plate incorporation and preincubation tests. The protective effects of LC in preincubation tests were slightly more than in plate incorporation tests. Both the DC and TM showed protective effects only in certain concentrations in some strains in either plate or preincubation tests. Thus the above results indicate that LC showed more protective effects in Salmonella strains TA97a, TA98, TA100 and TA102 than either DC or TM.
Gupta
S
S
Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Calcutta, India.
Mukhopadhyay
A
A
Ray
S
S
Giri
A K
AK
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002457:Cell Extracts / Q000494:pharmacology; D002486:Centchroman / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000737:chemistry; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D051381:Rats; D012475:Salmonella / Q000187:drug effects* / Q000235:genetics; D013045:Species Specificity; D013237:Stereoisomerism; D013629:Tamoxifen / Q000494:pharmacology*
D016587:Antimutagenic Agents; D002457:Cell Extracts; D009153:Mutagens; D013629:Tamoxifen; D002486:Centchroman