Siddique Yasir Hasan, Ara Gulshan, Beg Tanveer, Afzal Mohammad
Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002 (U.P.) India.
Life Sci. 2006 Dec 23;80(3):212-8. doi: 10.1016/j.lfs.2006.09.005. Epub 2006 Sep 16.
Medroxyprogesterone acetate was studied at three different concentrations (1, 5 and 10 microM), for its genotoxic effects in human peripheral blood lymphocyte culture using chromosomal aberrations and sister chromatid exchanges as parameters. Duplicate peripheral blood cultures were treated with three different concentrations (1, 5 and 10 microM) of medroxyprogesterone acetate. The study was carried out both in the absence as well as in the presence of metabolic activation (S9 mix) with and without NADP. Medroxyprogesterone acetate was found genotoxic at 5 and 10 microM in the presence of S9 mix with NADP. To study the possible mechanism of the genotoxicity of medroxyprogesterone acetate, superoxide dismutase and catalase at different doses were used separately and in combination with 10 microM of medroxyprogesterone at different doses in the presence of S9 mix with NADP. Superoxide dismutase treatment results in an increase of the genotoxic damage but catalase treatment reduce the genotoxic damage of medroxyprogesterone acetate. Catalase treatment in combination with superoxide dismutase also results in the further reduction of the genotoxic damage. The results of the present study reveal that medroxyprogesterone acetate is genotoxic only in the presence of metabolic activation (S9 mix) with NADP. Treatments with superoxide dismutase and catalase suggests the possible generation of reactive oxygen species by redox cycling of various forms of quinones, similar to estrogens, that are the results of aromatic hydroxylation by cytochrome P450s.
研究了醋酸甲羟孕酮在三种不同浓度（1、5和10微摩尔）下，以染色体畸变和姐妹染色单体交换为参数，对人外周血淋巴细胞培养物的遗传毒性作用。用三种不同浓度（1、5和10微摩尔）的醋酸甲羟孕酮处理外周血重复培养物。该研究在有无代谢活化（S9混合物）以及有无烟酰胺腺嘌呤二核苷酸磷酸（NADP）的情况下进行。发现醋酸甲羟孕酮在有NADP的S9混合物存在时，在5和10微摩尔浓度下具有遗传毒性。为了研究醋酸甲羟孕酮遗传毒性的可能机制，在有NADP的S9混合物存在的情况下，分别使用不同剂量的超氧化物歧化酶和过氧化氢酶，并将它们与不同剂量的10微摩尔醋酸甲羟孕酮联合使用。超氧化物歧化酶处理导致遗传毒性损伤增加，但过氧化氢酶处理减少了醋酸甲羟孕酮的遗传毒性损伤。过氧化氢酶与超氧化物歧化酶联合处理也导致遗传毒性损伤进一步降低。本研究结果表明，醋酸甲羟孕酮仅在有NADP的代谢活化（S9混合物）存在时具有遗传毒性。超氧化物歧化酶和过氧化氢酶的处理表明，类似于雌激素，各种形式的醌通过细胞色素P450s的芳香族羟基化产生的氧化还原循环可能会产生活性氧物种。
