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Genotoxic effects of drospirenone and ethinylestradiol in human breast cells (in vitro) and bone marrow cells of female mice (in vivo)
Drug and Chemical Toxicology ( IF 2.1 ) Pub Date : 2020-11-04 , DOI: 10.1080/01480545.2020.1843473
Arshad H Mir 1 , Vinod K Dumka 1 , Faheem Sultan 1 , Milindmitra K Lonare 1
Affiliation  

Abstract

Estrogen and progesterone congeners as found in various oral contraceptive formulations have been implicated as the cause of cancer in sex and tissue-specific targets. The mechanism of carcinogenesis by sex steroids is still debatable. In this study, we evaluated the genotoxicity induced by two components of one of the commonly used oral contraceptive formulation; drospirenone and ethinylestradiol in human breast cells (MCF-7) in vitro and in bone marrow cells of female mice in vivo. DNA damage was assessed by alkaline comet assay. Both of the drugs produced DNA damage in human breast cells at exposure concentrations which are about 100-fold and above than normally found in human blood after their lowest recommended doses. The DNA damage was produced only after metabolic activation by mice liver S-9 fraction in both cases. The co-exposure with both the compounds at median exposure levels resulted in potentiation of DNA damage. In bone marrow cells of adult female mice, both the compounds produced DNA damage at human equivalent doses after exposure was carried out repeatedly for approximately one estrus cycle (5 days). The co-administration with the compounds resulted in potentiation of DNA damage as indicated by percent tail DNA in comet assay. Thus it is concluded that drospirenone and ethinylestradiol cause DNA damage in certain target specific tissue (mammary epithelial cells) and in female bone marrow cells. The co-exposure with drospirenone and ethinylestradiol results in potentiation of genotoxicity which may pose a threat of cancer development in women taking these drugs for long periods.



中文翻译:

屈螺酮和炔雌醇对人乳腺细胞(体外)和雌性小鼠骨髓细胞(体内)的遗传毒性作用

摘要

在各种口服避孕药配方中发现的雌激素和孕激素同系物已被认为是性和组织特异性靶标癌症的原因。性类固醇致癌的机制仍有争议。在这项研究中,我们评估了一种常用口服避孕药制剂的两种成分引起的遗传毒性;体外人类乳腺细胞 (MCF-7)和体内雌性小鼠骨髓细胞中的屈螺酮和炔雌醇. DNA损伤通过碱性彗星试验评估。这两种药物在人体乳腺细胞中产生的 DNA 损伤,其最低推荐剂量后的暴露浓度是人体血液中正常浓度的 100 倍或以上。在这两种情况下,仅在小鼠肝脏 S-9 部分的代谢激活后才产生 DNA 损伤。在中等暴露水平下与这两种化合物共同暴露导致 DNA 损伤的增强。在成年雌性小鼠的骨髓细胞中,这两种化合物在暴露于人类等效剂量后产生 DNA 损伤,重复进行大约一个发情周期(5 天)。如彗星试验中尾DNA百分比所示,与化合物共同给药导致DNA损伤增强。因此得出结论,屈螺酮和炔雌醇会导致某些特定靶标组织(乳腺上皮细胞)和女性骨髓细胞中的 DNA 损伤。与屈螺酮和炔雌醇的共同暴露导致基因毒性增强,这可能对长期服用这些药物的女性构成癌症发展的威胁。

更新日期:2020-11-04
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