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Metabolism of the environmental toxicant benzo(a)pyrene by subcellular fractions of human ovary

机译:人卵巢亚细胞部分代谢环境有毒物质苯并(a)py

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Knowledge of the ability of the female reproductive system to metabolize environmental chemicals is critical not only from the standpoint of toxicity but also from infertility risk assessment. Benzo(a)pyrene (BaP) is a toxicant that is released into the environment from automobile exhausts, cigarette smoke, burning of refuse, industrial emissions, and hazardous waste sites. In exposed animals, BaP becomes activated to reactive metabolites that interfere with target organ function and as a consequence cause toxicity. Studies on animal models conducted in our laboratories and those of others have shown that BaP possess endocrine disrupting properties. Thus, this chemical has the potential to cause infertility and cancers in the female genital tract. An understanding of BaP metabolism in the female reproductive system will be of importance in the diagnosis and management of female fertility as well as cancers in the reproductive tissues. Therefore, the objective of our study was to examine the metabolism of BaP by human ovarian subcellular fractions. Human ovary samples (eight individuals) were obtained from postoperative tissue removed from subjects with uterine tumors. Subcellular fractions (nuclear, cytosolic, mitochondrial, and microsomal) were prepared by differential centrifugation. BaP (1 μM and 3 μM) was individually incubated with individual subcellular fractions for 15 min and the products were analyzed by high-performance liquid chromatography. Among the different fractions tested, microsomal BaP metabolism was higher than the rest of the fractions. The BaP metabolites identified were as follows: BaP-9,10-diol, BaP-4,5-diol, BaP-7,8-diol, 9(OH) BaP, 3(OH) BaP, BaP-1,6-dione, BaP-3,6-dione, and BaP-6,12-dione. Of interest was the presence of DNA-reactive metabolites such as BaP-3,6-dione, BaP-6,12-dione, and BaP 7,8-diol, which have been implicated in the causation of infertility and cancer. Our results indicate that women who are exposed to BaP via cigarette smoke, occupational settings, and diet are more likely at a larger risk of this toxicant-induced infertility and cancer than others.
机译:女性生殖系统代谢环境化学物质的能力的知识不仅从毒性的角度而且对于不孕风险评估也至关重要。苯并(a)re(BaP)是一种有毒物质,会从汽车尾气,香烟烟雾,垃圾焚烧,工业废气和危险废物场所释放到环境中。在暴露的动物中,BaP被活化为反应性代谢物,从而干扰目标器官的功能并因此引起毒性。在我们实验室及其他实验室进行的动物模型研究表明,BaP具有内分泌干扰特性。因此,这种化学物质有可能在女性生殖道中引起不育和癌症。对女性生殖系统中BaP代谢的理解对于女性生育力以及生殖组织中的癌症的诊断和管理至关重要。因此,我们研究的目的是检查人卵巢亚细胞组分对BaP的代谢作用。从患有子宫肿瘤的受试者的术后组织中获得人卵巢样品(八个人)。通过差异离心制备亚细胞级分(核,胞质,线粒体和微粒体)。将BaP(1μM和3μM)与各个亚细胞级分分别孵育15分钟,然后通过高效液相色谱法分析产物。在测试的不同部分中,微粒体BaP代谢高于其余部分。鉴定出的BaP代谢物如下:BaP-9,10-二醇,BaP-4,5-二醇,BaP-7,8-二醇,9(OH)BaP,3(OH)BaP,BaP-1,6- Dione,BaP-3,6-dione和BaP-6,12-dione。令人感兴趣的是存在DNA反应性代谢物,例如BaP-3,6-dione,BaP-6,12-dione和BaP 7,8-diol,它们与不育和癌症的发生有关。我们的结果表明,通过香烟烟雾,职业环境和饮食暴露于BaP的女性比其他女性更容易遭受这种由毒物引起的不育和癌症。

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