Concurrent increase of oxidative DNA damage and lipid peroxidation together with mitochondrial DNA mutation in human lung tissues during aging - Smoking enhances oxidative stress on the aged tissues

Concurrent increase of oxidative DNA damage and lipid peroxidation together with mitochondrial DNA mutation in human lung tissues during aging - Smoking enhances oxidative stress on the aged tissues
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DOI:
10.1006/abbi.1998.1036
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发表时间:
1999-02-15
影响因子:
3.9
通讯作者:
Wei, YH
Wei, YH
中科院分区:
生物学3区
文献类型:
--
作者:
Lee, HC;Lim, MLR;Wei, YH

文献摘要

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虽然已经确定人体组织中线粒体DNA(mtDNA)突变与内在衰老相关,但环境因素对人体组织中mtDNA突变和氧化DNA损伤的形成和积累的影响知之甚少。我们研究了不同年龄吸烟者和非吸烟者肺组织中线粒体DNA 4977 bp缺失和A3243 G点突变、氧化性DNA损伤(由8-羟基-2 '-脱氧鸟苷(8-OH-dG)的形成指示)和脂质过氧化物的水平。结果表明,人肺线粒体DNA 4977 bp缺失(P < 0.001)、8-OH-dG(P < 0.05)和脂质过氧化物(P <0.05)均随年龄增加而增加。在60岁以上的受试者中,吸烟者比非吸烟者有更广泛的DNA损伤和脂质过氧化。然而,吸烟者与年龄匹配的非吸烟者相比,其肺中4977 bp缺失和A3243 G点突变的mtDNA水平无显著差异。总之,这些结果表明,积累的线粒体DNA与4977 bp的缺失与氧化性DNA损伤和脂质过氧化物与衰老和吸烟增强人肺组织的氧化损伤。(C)北京:科学出版社.
Although mutation of mitochondrial DNA (mtDNA) in human tissues has been established to associate with intrinsic aging, the impact of environmental factors on the formation and accumulation of mtDNA mutations and oxidative DNA damage in human tissues is poorly understood. We have investigated the levels of mtDNA with the 4977-bp deletion and A3243G point mutation, oxidative DNA damage (indicated by the formation of 8-hydroxy-2'-deoxyguanosine, 8-OH-dG), and lipid peroxides in lung tissues from smokers and nonsmokers of subjects of different ages. The results showed concurrent age-dependent increase of the 4977-bp deleted mtDNA (P < 0.001), 8-OH-dG: (P < 0.05), and lipid peroxides (P < 0.05) in the human lung. In the group of subjects above 60 years old, smokers had more extensive DNA damage and lipid peroxidation than did the nonsmokers. However, the levels of mtDNA with the 4977-bp deletion and A3243G; point mutation in the lung of smokers were not significantly different from those of the age-matched nonsmokers. Taken together, these results suggest that accumulation of mtDNA with the 4977-bp deletion together with oxidative DNA damage and lipid peroxides is associated with aging and that smoking enhances oxidative damage in human lung tissues. (C) 1999 Academic Press.