Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.44 (AGT)
 770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were done to show whether a G to T mis-sense mutation at the third base of codon 249 of the p53 tumour suppressor gene is a 'hot spot' of aflatoxin attack as suggested by the results of epidemiological studies. Liver tissue from liver cancer patients in Taiwan and Japan was analysed for the presence of aflatoxin-DNA adducts (ADA) as a marker for aflatoxin exposure and an AGG to AGT transversion at codon 249 of the p53 gene. Ten per cent of samples containing ADA, indicating definite exposure of the subjects to aflatoxin, was found to harbour the codon 249 mutation, whereas 18% of the samples with no detectable adducts also contained the mutation. Our data do not support the hypothesis that codon 249 of the p53 gene DNA is a hot spot for aflatoxin mutagenesis as a 'late stage event' in human hepatocellular carcinogenesis.
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PMID:Recent aflatoxin exposure and mutation at codon 249 of the human p53 gene: lack of association. 766 37

Hemochromatosis and Wilson disease (WD), characterized by the excess hepatic deposition of iron and copper, respectively, produce oxidative stress and increase the risk of liver cancer. Because the frequency of p53 mutated alleles in nontumorous human tissue may be a biomarker of oxyradical damage and identify individuals at increased cancer risk, we have determined the frequency of p53 mutated alleles in nontumorous liver tissue from WD and hemochromatosis patients. When compared with the liver samples from normal controls, higher frequencies of G:C to T:A transversions at codon 249 (P < 0.001) and C:G to A:T transversions and C:G to T:A transitions at codon 250 (P < 0.001 and P < 0.005) were found in liver tissue from WD cases, and a higher frequency of G:C to T:A transversions at codon 249 (P < 0.05) also was found in liver tissue from hemochromatosis cases. Sixty percent of the WD and 28% of hemochromatosis cases also showed a higher expression of inducible nitric oxide synthase in the liver, which suggests nitric oxide as a source of increased oxidative stress. A high level of etheno-DNA adducts, formed from oxyradical-induced lipid peroxidation, in liver from WD and hemochromatosis patients has been reported previously. Therefore, we exposed a wild-type p53 TK-6 lymphoblastoid cell line to 4-hydroxynonenal, an unsaturated aldehyde involved in lipid peroxidation, and observed an increase in G to T transversions at p53 codon 249 (AGG to AGT). These results are consistent with the hypothesis that the generation of oxygen/nitrogen species and unsaturated aldehydes from iron and copper overload in hemochromatosis and WD causes mutations in the p53 tumor suppressor gene.
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PMID:Increased p53 mutation load in nontumorous human liver of wilson disease and hemochromatosis: oxyradical overload diseases. 1105 Jan 62