Molecular mechanisms of oxidative stress-induced carcinogenesis: from epidemiology to oxygenomics.
Oxidative stress is associated with inflammation, radiation, reperfusion, and iron overload. Epidemiological observations have shown that oxidative stress is one of the major sources of carcinogenesis, the top-ranked cause of human mortality worldwide. In situations of oxidative stress, reactive oxygen and nitrogen species contribute to the alteration of genome information, presumably followed by selection of the adapted proliferating cells in a given environment. Recent data suggest that common molecular mechanisms exist in oxidative stress-induced carcinogenesis, including p16(INK4A) inactivation. Thus far, oxidative DNA damage in the genome as a cause of mutation has been recognized to be randomly distributed based on in vitro experiments, while localization of oxidative DNA damage in vivo has not been pursued. However, using a novel technique based on DNA immunoprecipitation in combination with genome information, we now know that the localization of oxidative DNA damage is not random in vivo. We propose to call this rather novel research area "oxygenomics." Many signaling pathways start from the recognition of DNA damage. Thus, possible underlying principles should be elucidated in association with each cell type, the genomic location of the damage with its transcriptional activity as well as the chromatin status determining the epigenetic effect.
Toyokuni
Shinya
S
Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan. toyokuni@path1.med.kyoto-u.ac.jp
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D049109:Cell Proliferation; D002875:Chromosomes; D004249:DNA Damage; D004260:DNA Repair; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D007249:Inflammation; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species
D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009584:Nitrogen