Mechanism of Oxidative DNA Damage Induced by Environmental Carcinogens and Antioxidants

Abstract

Modification 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 32P-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 32P-labeled DNA fragments. This review shows recent experimental results and discusses the mechanisms of oxidative DNA damage in relation to carcinogenesis.