Prooxidant States and Tumor Promotion

• Published in: Science (American Association for the Advancement of Science) Vol. 227; no. 4685; pp. 375 - 381
• Main Author: Cerutti, Peter A.
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 25-01-1985; American Association for the Advancement of Science
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Biological and medical sciences; Cancer; Cancer research; Carcinogenesis; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens - metabolism; Carcinogens - pharmacology; Cations - metabolism; Cell Differentiation; Cell Division; Cell Line; Cell Membrane - physiology; Cell Transformation, Neoplastic; Chromosome Aberrations; Chromosomes - drug effects; Cytochrome P-450 Enzyme System - metabolism; DNA - metabolism; DNA damage; Electron Transport; Embryonic cells; Epidermal cells; Fibroblasts; Gene expression; Gene Expression Regulation; General aspects; Genetic research; Humans; Hydrogen Peroxide - metabolism; Hydroxides - metabolism; Hydroxyl Radical; Lipid Peroxides - metabolism; Lymphocytes; Medical sciences; Microbodies - metabolism; Mutation; Neoplasms - chemically induced; Observations; Oncology, Experimental; Oxidation-Reduction; Oxygen - metabolism; Oxygen - physiology; Peroxides; Poly Adenosine Diphosphate Ribose - metabolism; Reactive oxygen species; Singlet Oxygen; Sulfhydryl Compounds - physiology; Superoxides - metabolism; Tumors; Ultraviolet Rays; Chromosomal aberration; Oxygen; Carcinogenesis promotion; DNA
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2981433

There is convincing evidence that cellular prooxidant states--that is, increased concentrations of active oxygen and organic peroxides and radicals--can promote initiated cells to neoplastic growth. Prooxidant states can be caused by different classes of agents, including hyperbaric oxygen, radiation, xenobiotic metabolites and Fenton-type reagents, modulators of the cytochrome P-450 electron-transport chain, peroxisome proliferators, inhibitors of the antioxidant defense, and membrane-active agents. Many of these agents are promoters or complete carcinogens. They cause chromosomal damage by indirect action, but the role of this damage in carcinogenesis remains unclear. Prooxidant states can be prevented or suppressed by the enzymes of the cellular antioxidant defense and low molecular weight scavenger molecules, and many antioxidants are antipromoters and anticarcinogens. Finally, prooxidant states may modulate the expression of a family of prooxidant genes, which are related to cell growth and differentiation, by inducing alterations in DNA structure or by epigenetic mechanisms, for example, by polyadenosine diphosphate--ribosylation of chromosomal proteins.