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饮酒如何致癌?科学家首次揭示酒精会损伤造血干细胞
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Topic: 饮酒如何致癌?科学家首次揭示酒精会损伤造血干细胞 (Read 96 times)
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饮酒如何致癌?科学家首次揭示酒精会损伤造血干细胞
January 05, 2018, 03:59:52 AM
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过量饮酒的代价不光是宿醉和伤身那么简单。剑桥大学的一项最新研究结果显示,饮酒会“损伤”干细胞,从而提高罹患癌症的风险。
在世界卫生组织国际癌症研究中心(IARC)的1类致癌物清单上,酒精位列其中。英国的一项研究指出,该国4%的癌症由酒精引起,也就相当于每年12800人因酒精患癌。然而,饮酒究竟如何致癌,此前并没有明确的分子机制证明两者间的关联。
英国剑桥大学MRC分子生物学实验室Ketan Patel教授及其同事最新的一项研究指出,酒精可以损伤干细胞的DNA,从而增加癌症发生几率。这是科学家首次揭开饮酒和癌症之间的关联,该成果于1月4日凌晨发表在国际顶级学术期刊《自然》(Nature)。
研究描述的“损伤”主要发生在造血干细胞中。研究人员通过染色体分析和DNA测序发现,酒精的初级代谢产物乙醛会导致小鼠造血干细胞DNA双链断裂。此前已有研究证实,在体外细胞培养试验中,乙醛的确会导致癌症。
论文指出,虽然部分DNA断裂随后被修复,但是残留损害仍影响广泛,包括某些区域被删除,染色体重排。而这些遗传变化接下来会被传递到无数源自这些造血干细胞的后代。具有自我更新的能力的造血干细胞能分化为各种血细胞前体细胞,最终生成各种血细胞成分,包括红细胞、白细胞和血小板。
Patel表示,“一些癌症发展的源头就在于DNA损伤,虽然这些损伤通常是偶然发生,但我们的研究可以证明,饮酒会增加DNA损害的风险。”
当然,对大多数人来说,乙醛这种代谢产物往往是身体的“过客”, 会被乙醛脱氢酶2(Aldh2)氧化为醋酸盐。但研究人员在小鼠实验中进一步发现,对丧失乙醛脱氢酶的小鼠被给予酒精时,其细胞中DNA损伤是正常小鼠的四倍。
上述结论意味着,对人体而言,能否借助乙醛脱氢酶有效清除酒精至关重要。但研究人员指出,部分人群会携带两种突变基因,即Aldh2和Fancd2,这会让他们更易受到酒精影响,最直接的表现则是身体不适。以亚洲人为例,约有5.4亿人口携带一种Aldh2基因突变,导致他们无法降解乙醛。
Patel补充说,“我们这项研究强调的是,身体不能有效清除酒精会导致酒精相关的DNA损伤风险增加,从而也就导致相应的癌症。但重要的还有,酒精清除和DNA修复系统并不完美,酒精仍然可以以不同的方式导致癌症,即使在防御机制完好无损的人群中。”
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