Genotoxic potential of ethinylestradiol in cultured mammalian cells.
Ethinylestradiol, a steroidal estrogen, is widely used with various progestogens in oral contraceptives formulations. There are sufficient evidences for the carcinogenicity of ethinylestradiol in experimental animals. The reports on the genotoxic potential of ethinylestradiol are contradictory. Here in the present study we have tested the genotoxicity of ethinylestradiol in human lymphocytes using chromosomal aberrations (CAs), mitotic index (MI) and sister chromatid exchanges (SCEs) as a parameter. The study was carried out in the absence, as well as in the presence, of rat liver microsomal fraction, with and without NADP. Ethinylestradiol was studied at three different concentrations (1, 5 and 10 microM) and was found non-genotoxic in the absence of metabolic activation (S9 mix) and in S9 mix without NADP. Ethinylestradiol was found to be genotoxic at 5 and 10 microM in the presence of S9 mix with NADP. To study the possible mechanism of the genotoxicity of ethinylestradiol, superoxide dismutase (SOD) and catalase (CAT) were used separately and in combination along with 10 microM of ethinylestradiol at different doses. SOD treatment increased CAs and SCEs and decreases MI as compared with treatment with 10 microM of ethinylestradiol alone in the presence of S9 mix with NADP at both of the tested doses. CAT treatment decreased the frequencies of CAs and SCEs and increased MI, as compared with treatment with 10 microM of ethinylestradiol alone in the presence of S9 mix with NADP. CAT treatment in combination with SOD also decreased the frequencies of CAs and SCEs and increased MI suggesting a possible role of reactive oxygen species for the genotoxic damage.
Siddique
Yasir Hasan
YH
Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India. yasir_hasansiddique@rediffmail.com
Beg
Tanveer
T
Afzal
Mohammad
M
D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects; D004967:Estrogens / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009152:Mutagenicity Tests; D017382:Reactive Oxygen Species / Q000378:metabolism; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology
D004967:Estrogens; D017382:Reactive Oxygen Species; D004997:Ethinyl Estradiol; D002374:Catalase; D013482:Superoxide Dismutase