title: Role of oxidative stress in non-genotoxic carcinogenesis with special reference to liver tumors induced by peroxisome proliferators.
abstract: Peroxisome proliferators (POPs), such as hypolipidemic drugs or industrial phthalate ester plasticizers, are widely known as non-genotoxic hepatocarcinogens in rodents. As one of the possible mechanisms of POP-induced carcinogenesis, the "Oxidative Stress" theory has been postulated. In this review, in order to reconsider the significance of "Oxidative Stress" to POP-induced carcinogenesis, we focus on in vivo studies examining formation of 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage with mutagenic potential, after treatment of rodents with POPs. Some studies clearly demonstrated that 8-OH-dG levels in the liver DNA were increased by POP-treatments. These findings suggest that "Oxidative Stress" could contribute as one factor to POP-induced carcinogenesis. Furthermore, we refer to other multiple biological changes caused by POP-treatment presumably contributing to the carcinogenic mechanisms, and consider possible roles of "Oxidative Stress" in the carcinogenesis process.
authors.affiliation: Division of Toxicology, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sai-Kato
authors.forename: A
authors.initials: A
authors.lastname: Takagi
authors.forename: T
authors.initials: T
authors.lastname: Umemura
authors.forename: R
authors.initials: R
authors.lastname: Hasegawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kurokawa
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008830:Microbodies / Q000187:drug effects*; D018384:Oxidative Stress
chemical_list: D002273:Carcinogens; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine