著者

Shinji Oikawa

出版者

The Japanese Environmental Mutagen Society

雑誌

Genes and Environment (ISSN:18807046)

巻号頁・発行日

vol.30, no.1, pp.1-9, 2008 (Released:2008-03-25)

参考文献数

61

被引用文献数

1 3

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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.

著者

Keiko Inami Masataka Mochizuki

出版者

The Japanese Environmental Mutagen Society

雑誌

Genes and Environment (ISSN:18807046)

巻号頁・発行日

vol.30, no.3, pp.71-76, 2008 (Released:2008-09-09)

参考文献数

12

被引用文献数

2 2

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2-Acetylaminofluorene (AAF) is a procarcinogen and its activation mechanisms have been investigated in detail. AAF was metabolized to 2-acetylamino-9-fluorenone (AAF=O) and 2-acetylamino-9-fluorenol by S9 mix. The mutagenicity of AAF=O in the presence of S9 mix was equal in potency to that of AAF in Salmonella typhimurium TA1538, but the activation mechanism of AAF=O was poorly reported. In this study, we investigated possible ultimate species derived from AAF=O; N-hydroxy-2-acetylamino-9-fluorenone (N-OH-AAF=O), N-acetoxy-2-acetylamino-9-fluorenone (N-OAc-AAF=O), N-hydroxy-2-amino-9-fluorenone (N-OH-AF=O), and N-acetoxy-2-trifluoroacetylamino-9-fluorenone (N-OAc-TFAAF=O), a model compound for N-acetoxy-2-amino-9-fluorenone (N-OAc-AF=O), were synthesized and their mutagenicity was examined in S. typhimurium TA1538. The activation mechanism in S. typhimurium TA1538 was also investigated. The compounds in order of decreasing mutagenicity are N-OAc-TFAAF=O>N-OH-AF=O>N-OAc-AAF=O> N-OH-AAF=O. AAF=O is at least partially responsible for the mutagenicity of AAF, since a small amount of AAF is oxidized to AAF=O in the presence of S9 mix. Furthermore we suggest that an ultimate active species of AAF=O in S. typhimurium is N-OAc-AF=O, with the same activation manner as AAF.