THE EFFECTS OF HYDROGEN-PEROXIDE ON DNA-REPAIR ACTIVITIES
THE EFFECTS OF HYDROGEN-PEROXIDE ON DNA-REPAIR ACTIVITIES
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DOI：
10.1016/0921-8777(94)00054-a
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发表时间：
1995-03-01
期刊：
影响因子：
--
通讯作者：
ROUSH, GC
中科院分区：
文献类型：
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作者：
HU, JJ;DUBIN, N;ROUSH, GC
由H2 O2产生的氧自由基参与多阶段致癌过程;机制包括致癌物活化、氧化DNA损伤和肿瘤促进。在这项研究中，我们评估了另一个潜在的机制H2 O2在致癌-调节DNA修复活动。人外周血单个核白细胞预暴露于H2 O2显着抑制DNA修复活动的N-甲基-N '-硝基-N-亚硝基胍诱导的损伤，测量为非程序性DNA合成。在4名健康受试者中比较了不同日期的两种样品制备液对H2 O2的反应。多变量一般线性模型的结果表明，H2 O2显着抑制DNA修复的剂量依赖性的方式调整后，受试者之间和受试者内的变异。H2 O2处理每单位（μ M）增加诱导的程序外DNA合成估计减少5.0单位（dpm/5 × 10（5）个细胞）。此外，无论H2 O2剂量水平如何，在不同日期采样的同一个体的DNA修复活性存在显著差异。结果表明，H_2O_2不仅能引起DNA损伤，而且对DNA修复有抑制作用。
Oxygen free radicals generated by H2O2 are involved in the multistage carcinogenic process; mechanisms include carcinogen activation, oxidative DNA damage, and tumor promotion. In this study, we have evaluated another potential mechanism of H2O2 in carcinogenesis-modulation of DNA repair activities. Preexposure of human peripheral mononuclear leukocytes to H2O2 significantly inhibited DNA repair activities in response to damage induced by N-methyl-N'-nitro-N-nitrosoguanidine, measured as unscheduled DNA synthesis. The responses to H2O2 were compared in four healthy human subjects with two sample preparations on different days. Results from multivariate general linear models showed that H2O2 significantly inhibited DNA repair in a dose-dependent manner after adjustment for between- and within-subject variabilities. There was an estimate of 5.0 units (dpm/5 X 10(5) cells) decrease in induced unscheduled DNA synthesis per unit (mu M) increase of H2O2 treatment. Furthermore, there was substantial variability in DNA repair activities for the same individual sampled on different days regardless of H2O2 dose level. Results from this study suggest that H2O2 not only can induce DNA damage, but also have suppressive effects on DNA repair.