Article: article from journal or magazin.
Transition mutation in codon 248 of the p53 tumor suppressor gene induced by reactive oxygen species and a nitric oxide-releasing compound.
Souici A.C. a repris son nom Peyter, AC
Exposing the human bronchial epithelial cell line BEAS-2B to the nitric oxide (NO) donor sodium 1-(N,N-diethylamino)diazen-1-ium-1, 2-diolate (DEA/NO) at an initial concentration of 0.6 mM while generating superoxide ion at the rate of 1 microM/min with the hypoxanthine/xanthine oxidase (HX/XO) system induced C:G-->T:A transition mutations in codon 248 of the p53 gene. This pattern of mutagenicity was not seen by 'fish-restriction fragment length polymorphism/polymerase chain reaction' (fish-RFLP/PCR) on exposure to DEA/NO alone, however, exposure to HX/XO led to various mutations, suggesting that co-generation of NO and superoxide was responsible for inducing the observed point mutation. DEA/NO potentiated the ability of HX/XO to induce lipid peroxidation as well as DNA single- and double-strand breaks under these conditions, while 0.6 mM DEA/NO in the absence of HX/XO had no significant effect on these parameters. The results show that a point mutation seen at high frequency in certain common human tumors can be induced by simultaneous exposure to reactive oxygen species and a NO source.
Antigens, Polyomavirus Transforming/physiology, Bronchi/cytology, Cell Line, Transformed, Codon/chemistry, Codon/genetics, DNA Damage, DNA Fragmentation, Drug Synergism, Epithelial Cells/chemistry, Epithelial Cells/cytology, Genes, p53/drug effects, Genes, p53/genetics, Humans, Hydrazines/pharmacology, Hydrazines/toxicity, Hypoxanthine/metabolism, Lipid Peroxidation, Nitric Oxide/metabolism, Nitric Oxide Donors/pharmacology, Nitric Oxide Donors/toxicity, Nitrogen Oxides, Point Mutation, Reactive Oxygen Species, Superoxides/metabolism, Xanthine Oxidase/metabolism
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