The role of superoxide dismutase and gene amplification in carcinogenesis.
Chemical carcinogenesis is hypothesized to involve manganese superoxide dismutase and gene amplification. Initiation is hypothesized to be caused by destruction of the DNA that enables the cell to induce manganese superoxide dismutase. Tumor promotion then causes amplification of the manganese superoxide dismutase gene and the cell proliferation gene (oncogene) because of selective pressure exerted by the promoter. Because the promoter causes cell division and chromosomal rearrangements, unequal segregation of the amplified genes results. Because cells which have high amounts of the cell proliferation gene and low amounts of the manganese superoxide dismutase gene grow faster, these cells become dominant and a tumor forms.
D000818:Animals; D002273:Carcinogens / Q000009:adverse effects; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D002472:Cell Transformation, Viral; D004351:Drug Resistance; D004790:Enzyme Induction / Q000187:drug effects; D005784:Gene Amplification; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced* / Q000235:genetics; D009857:Oncogenes / Q000187:drug effects; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D002273:Carcinogens; D013482:Superoxide Dismutase; D008727:Methotrexate