Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins
Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins
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DOI：
10.1126/science.1059501
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发表时间：
2001-06-15
期刊：
影响因子：
56.9
通讯作者：
Blair, IA
中科院分区：
文献类型：
--
作者：
Lee, SH;Oe, T;Blair, IA
流行病学数据表明，饮食中的抗氧化剂对癌症有保护作用。这导致了一种建议，即膳食补充抗氧化剂，如维生素C（vit C）可能有助于预防疾病。然而，维生素C已被证明是无效的癌症化学预防研究。此外，人们对潜在有害的过渡金属离子介导的促氧化作用表示担忧。我们现在已经确定，维生素C诱导脂质过氧化氢分解为DNA反应性双功能亲电体4-氧代-2-壬烯醛、4，5-环氧-2（E）-癸烯醛和4-羟基-2-壬烯醛。化合物4，5-环氧-2（E）-癸烯醛是乙烯基-2 '-脱氧腺苷的前体，乙烯基-2'-脱氧腺苷是在人类DNA中发现的高度致突变性损伤。维生素C介导的遗传毒素的形成，从脂质过氧化氢在过渡金属离子的情况下，可以帮助解释其缺乏作为癌症化学预防剂的功效。
Epidemiological data suggest that dietary antioxidants play a protective role against cancer. This has led to the proposal that dietary supplementation with antioxidants such as vitamin C (vit C) may be useful in disease prevention. However, vit C has proved to be ineffective in cancer chemoprevention studies. In addition, concerns have been raised over potentially deleterious transition metal ion-mediated pro-oxidant effects. We have now determined that vit C induces lipid hydroperoxide decomposition to the DNA-reactive bifunctional electrophiles 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal, and 4-hydroxy-2-non-enal, The compound 4,5-Epoxy-2(E)-decenal is a precursor of etheno-2'-deoxyadenosine, a highly mutagenic lesion found in human DNA. Vitamin C-mediated formation of genotoxins from lipid hydroperoxides in the absence of transition metal ions could help explain its lack of efficacy as a cancer chemoprevention agent.