Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromatosis: Oxyradical overload diseases

摘要: Hemochromatosis and Wilson disease (WD), characterized by the excess hepatic deposition of iron copper, respectively, produce oxidative stress increase risk liver cancer. Because frequency p53 mutated alleles in nontumorous human tissue may be a biomarker oxyradical damage identify individuals at increased cancer risk, we have determined from WD hemochromatosis patients. When compared with samples normal controls, higher frequencies G:C to T:A transversions codon 249 (P < 0.001) C:G A:T transitions 250 0.001 P 0.005) were found cases, 0.05) also was cases. Sixty percent 28% cases showed expression inducible nitric oxide synthase liver, which suggests as source stress. A high level etheno-DNA adducts, formed oxyradical-induced lipid peroxidation, patients has been reported previously. Therefore, exposed wild-type TK-6 lymphoblastoid cell line 4-hydroxynonenal, an unsaturated aldehyde involved observed G T (AGG AGT). These results are consistent hypothesis that generation oxygen/nitrogen species aldehydes copper overload causes mutations tumor suppressor gene.