Mechanisms of tumor promotion by reactive oxygen species.
This review analyzes the available information concerning mechanisms of non-genotoxic action of reactive oxygen species (ROS) during tumor promotion and pathways of their generation under the influence of chemical compounds. Special attention is given to the ability of ROS to induce pseudohypoxia through inhibition of prolyl oxidase, which is an oxygen sensor in the cell. Functions of HIF-1alpha as a main contributor to the ROS-induced promotion are analyzed. Data suggest that an unregulated high level of HIF-1alpha in the cell could induce the development of tumors. Hypothetical possibilities of ROS production under the influence of different environmental pollutants, which are promoters of tumorigenesis, include functioning of cytochrome P450 during oxidation of substrates, functioning of the mitochondrial respiratory chain, and action of peroxisome proliferators.
Kobliakov
V A
VA
Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia. kobliakov@rambler.ru
D002273:Carcinogens / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002273:Carcinogens; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D003577:Cytochrome P-450 Enzyme System