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Environmental Hazard in the Aetiology of Somatic and Germ Cell Aneuploidy

机译:体细胞和生殖细胞非整倍性病因的环境危害

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摘要

Sources of environmental exposures to potentially aneugenic agents are many and include occupational and therapeutic exposures, and exposures associated with lifestyle habits. In this present study, some of these agents and exposure scenarios are discussed that involve potentially large population targets and/or seem to affect chromosome segregation by previously unsuspected mechanisms: metals, possibly acting by epigenetic mechanisms; nano-sized particles that might directly interact with subcellular components of the mitotic and meiotic machineries; cytostatic drugs in healthcare occupations; anticancer therapies potentially affecting the genetic integrity of gametes; continuously increasing electromagnetic field exposures with some sparse evidence of aneugenic activity; endocrine disruptors and their seemingly elusive effects in mouse oocytes, including the first evidence that prenatal exposure could affect meiotic nondisjunction in adult life. Hazards are considered for both somatic cells at risk of neoplastic transformation or tumour progression by chromosome loss and gain and germ cells at risk of heritable aneuploidies associated with spontaneous abortions or genetic diseases. Finally, possible synergistic interactions between environmental exposure and ageing or genetic predisposition are considered that could influence ultimate risks.
机译:潜在的致癌物质导致环境暴露的来源很多,包括职业和治疗暴露以及与生活方式习惯有关的暴露。在本研究中,讨论了其中的某些因素和暴露情况,这些情况涉及潜在的大量人口目标和/或似乎通过以前未曾怀疑的机制影响染色体分离:金属,可能通过表观遗传机制起作用;可能直接与有丝分裂和减数分裂机制的亚细胞成分相互作用的纳米级颗粒;医疗保健行业中的细胞抑制药物;可能影响配子遗传完整性的抗癌疗法;不断增加电磁场的暴露,并有一些稀疏的气生活动证据;内分泌干​​扰物及其在小鼠卵母细胞中似乎难以捉摸的作用,包括第一个证据表明产前暴露可能影响成年后减数分裂的非分离。既考虑到因染色体丢失和染色体增生而处于发生肿瘤转化或肿瘤进展风险的体细胞,又考虑到与自然流产或遗传性疾病相关的可遗传非整倍性风险的生殖细胞。最后,认为环境暴露与衰老或遗传易感性之间可能存在的协同相互作用可能影响最终风险。

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