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Intraindividual variations of DNA adduct levels in humans

机译:人类DNA加合物水平的个体差异

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摘要

Reports on intraindividual changes of DNA adduct levels in humans are rare. Most of the data available in the literature are from polycyclic aromatic hydrocarbons (PAHs) and are measured in white blood cells with super(32) P -postlabeling or immunochemical assays. Surprisingly, environmental exposure can have a larger effect on PAH adduct levels than occupational exposure, food or smoking. Highest (13-fold) summer/winter increments, due to indoor heating were observed in Gliwice, Poland. Further studies of environmental PAH exposure confirm the environmental influence on intraindividual changes in PAHs-DNA adduct levels: studies of the Teplice program, (Czech Republic) and studies with US soldiers, stationed in Germany who went for a 8-week period of duty to Kuwait. Variations in occupational exposure, e.g., changing of anode material in aluminium plants (elevation factor 3.94), layoffs, reduced working hours in iron foundries or vacation also led to intraindividual changes in PAH adduct levels. Increase in PAH adduct levels after consumption of charcoal broiled meat evidently depends on individual susceptibility, e.g., polymorphism. In one person a 7.4-fold increment was observed. PAH adduct levels were not significantly influenced by smoking cessation whereas sister chromatid exchanges significantly decreased. Changes in occupational exposure to styrene in lamination plants, e.g., due to vacation, did not significantly influence styrene-O super(6)-dG adduct levels in lymphocytes and granulocytes as determined by super(32) P -postlabeling. Increase of N7-methylguanine and O super(6)-methylguanine levels were followed in white blood cells during treatment of cancer patients with dacarbazine and allowed insights into pharmacokinetic properties. According to a rough estimation the high increment in the PAHs-DNA adduct level of about 13 observed in Gliwice (see above) would result in a tentative increase in cancer risk from about 1 death/10 super(7) inhabitants to approximately 10 deaths/10 super(7) inhabitants which, in general, is considered as acceptable.
机译:关于人类DNA加合物水平的个体变化的报道很少。文献中可获得的大多数数据来自多环芳烃(PAHs),并通过super(32)P后标记或免疫化学分析在白细胞中进行测量。令人惊讶的是,与职业接触,食物或吸烟相比,环境接触对PAH加合物的影响更大。在波兰格利维采,由于室内取暖,夏季/冬季增幅最高(13倍)。进一步的环境PAH暴露研究证实了环境对PAHs-DNA加合物水平的个体变化的影响:Teplice计划的研究(捷克共和国)和与驻扎德国的美国士兵进行的研究,他们在德国工作了8周,科威特。职业暴露的变化,例如铝厂阳极材料的变化(升高系数3.94),裁员,铸铁厂工作时间的减少或休假,也导致PAH加合物含量的个别变化。食用木炭烤肉后,PAH加合物水平的增加显然取决于个体的易感性,例如多态性。在一个人中,观察到7.4倍的增量。戒烟对PAH加合物的水平没有显着影响,而姐妹染色单体的交换显着降低。叠层植物中职业暴露于苯乙烯的变化,例如由于休假,对super(32)P-postlabeling确定的淋巴细胞和粒细胞中苯乙烯-O super(6)-dG加合物的水平没有显着影响。在用达卡巴嗪治疗癌症患者期间,白细胞中的N7-甲基鸟嘌呤和O super(6)-甲基鸟嘌呤水平增加,并能深入了解药代动力学特性。根据粗略的估计,格利维采观察到的PAHs-DNA加合物水平的高增加(约13)(参见上文)将导致癌症风险从约1死亡/ 10 super(7)居民暂时增加到约10死亡/一般认为10个super(7)居民是可以接受的。

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