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Mechanism of Oxidative DNA Damage Induced by Environmental Carcinogens and Antioxidants

机译：环境致癌物和抗氧化剂引起的DNA氧化损伤机理

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摘要

Modication of DNA is believed to be a key step in mutagenesis and carcinogenesis. Reactive oxygen species (ROS) generated by environmental factors can cause oxidative DNA damage. This review focused on the role of oxidative DNA damage in mutagenesis and carcinogenesis mediated by environmental factors. This research investigated the mechanism of DNA damage induced by environmental chemicals and dietary factors using ~(32)P-labeled DNA fragments obtained from the c-Ha-RAS-1 protooncogene and the p16 and p53 tumor suppressor genes. In addition, the content of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) was measured by using a high performance liquid chromatograph equipped with an electrochemical detector. 8-oxodG is probably one of the most abundant DNA lesion formed during oxidative stress. Antioxidants are considered as the most promising chemopreventive agents against various human cancers.However, some antioxidants play paradoxical roles acting as “double-edged sword”. The present research also investigated the mechanism of DNA damage induced by antioxidants using human cultured cell lines and ~(32)P-labeled DNA fragments. This review shows recent experimental results and discusses the mechanisms of oxidative DNA damage in relation to carcinogenesis.
机译：DNA的治疗被认为是诱变和癌变的关键步骤。环境因素产生的活性氧（ROS）可能会导致DNA氧化损伤。这篇综述着重于氧化性DNA损伤在环境因素介导的诱变和致癌作用中的作用。这项研究使用了从c-Ha-RAS-1原癌基因以及p16和p53抑癌基因获得的〜（32）P标记的DNA片段，研究了环境化学物质和饮食因素诱导的DNA损伤机理。另外，通过使用配备有电化学检测器的高效液相色谱仪来测量8-氧代-7,8-二氢-2'-脱氧鸟苷（8-oxodG）的含量。 8-oxodG可能是氧化应激期间形成的最丰富的DNA损伤之一。抗氧化剂被认为是对抗各种人类癌症的最有前途的化学预防剂。但是，某些抗氧化剂起着“双刃剑”的反常作用。本研究还研究了使用人类培养的细胞系和〜（32）P标记的DNA片段，抗氧化剂诱导的DNA损伤机理。这项审查显示了最新的实验结果，并讨论了与致癌有关的氧化性DNA损伤的机制。

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