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通过碱性彗星试验检测内源性和合成雌性激素在外周血细胞中未诱导产生遗传毒性。

Lack of genotoxicity induced by endogenous and synthetic female sex hormones in peripheral blood cells detected by alkaline comet assay.

作者信息

Braz Mariana Gobbo, Salvadori Daisy Maria Favero

机构信息

Department of Pathology, School of Medicine, UNESP-São Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil.

出版信息

Environ Mol Mutagen. 2007 Jun;48(5):414-20. doi: 10.1002/em.20295.

Abstract

The etiology of hormone-induced cancers has been considered to be a combination of genotoxic and epigenetic events. Currently, the Comet assay is widely used for detecting genotoxicity because it is relatively simple, sensitive, and capable of detecting various kinds of DNA damage. The present study evaluates the genotoxic potential of endogenous and synthetic sex hormones, as detected by the Comet assay. Blood cells were obtained from 12 nonsmoking and 12 smoking women with regular menstrual cycles and from 12 nonsmoking women taking low-dose oral contraceptives (OC). Peripheral blood samples were collected at three phases of the menstrual cycle (early follicular, mean follicular, and luteal phases), or at three different moments of oral contraceptive intake. Three blood samples were also collected from 12 healthy nonsmoking men, at the same time as oral contraceptive users. Results showed no significant difference in the level of DNA damage among the three moments of the menstrual cycle either in nonsmoking and smoking women, or between them. No significant difference in DNA damage was also observed among oral contraceptive users, nonusers, and men. Together, these data indicate lack of genotoxicity induced by the physiological level of the female sex hormones and OC as assessed by the alkaline Comet assay. In conclusion, normal fluctuation in endogenous sex hormones and use of low-doses of oral contraceptive should not interfere with Comet assay data when this technique is used for human biomonitoring.

摘要

激素诱导的癌症病因被认为是基因毒性和表观遗传事件的综合作用。目前,彗星试验因其相对简单、灵敏且能够检测各种DNA损伤而被广泛用于检测基因毒性。本研究通过彗星试验评估内源性和合成性激素的基因毒性潜力。血细胞取自12名月经周期正常的非吸烟女性和12名吸烟女性,以及12名服用低剂量口服避孕药(OC)的非吸烟女性。在月经周期的三个阶段(卵泡早期、卵泡中期和黄体期)或口服避孕药摄入的三个不同时刻采集外周血样本。还在与口服避孕药使用者相同的时间从12名健康非吸烟男性中采集了三份血样。结果显示,无论是在非吸烟和吸烟女性中,还是在她们之间,月经周期的三个时刻的DNA损伤水平均无显著差异。在口服避孕药使用者、非使用者和男性之间,也未观察到DNA损伤的显著差异。总之,这些数据表明,通过碱性彗星试验评估,女性性激素和口服避孕药的生理水平不会诱导基因毒性。总之,当该技术用于人体生物监测时,内源性性激素的正常波动和低剂量口服避孕药的使用不应干扰彗星试验数据。

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