Evaluation of genotoxic potential of synthetic progestins-norethindrone and norgestrel in human lymphocytes in vitro
Ahmad, M.E.; Shadab, G.G.; Azfer, M.A.; Afzal, M.
Mutation Research 494(1-2): 13-20
2001
ISSN/ISBN: 0027-5107 PMID: 11423341 DOI: 10.1016/s1383-5718(01)00164-4Document Number: 261201
The genotoxicity study of two widely used contraceptive synthetic progestins, i.e. norgestrel and norethindrone was carried out on human lymphocyte chromosomes using chromosomal aberrations (CA), sister chromatid exchanges (SCE) and cell growth kinetics as parameters. The study was carried out both in the presence as well as in the absence of metabolic activation (S9 mix). The lymphocytes were exposed to three different concentrations of the drugs (20, 40 and 75 mug/ml for norethindrone and 10, 25 and 50 mug/ml for norgestrel) for three different durations (24, 48 and 72 h). The drug norethindrone was found to be non-genotoxic at any concentration and at any exposure duration either in the presence or in the absence of S9 mix. But another drug norgestrel was found to affect the genetic material. It induces CA, SCE at significant level, and inhibits lymphocyte proliferation at 25 and 50 mug/ml of concentrations only. In the presence of S9 mix the values obtained for CA, SCE and mitotic index (MI) were more significant. A time and dose relationship was also observed. It was concluded that norgestrel itself and possibly its metabolites are potent mutagens beyond a particular dose in human lymphocytes.