title: DNA damage induced by m-phenylenediamine and its derivative in the presence of copper ion.
abstract: To clarify the mechanism of carcinogenesis by hair dyes, we compared the extent of DNA damage induced by mutagenic m-phenylenediamine and 4-methoxy-m-phenylenediamine, using 32P-5'-end-labeled DNA fragments obtained from the human c-Ha-ras-1 protooncogene and the p53 tumor suppressor gene. Carcinogenic 4-methoxy-m-phenylenediamine caused DNA damage at thymine and cytosine residues in the presence of Cu(II). Catalase and bathocuproine, a Cu(I)-specific chelator, inhibited 4-methoxy-m-phenylenediamine-induced DNA damage, suggesting the involvement of H2O2 and Cu(I). Superoxide dismutase (SOD) enhanced the DNA damage. Formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) was induced by 4-methoxy-m-phenylenediamine in the presence of Cu(II). UV-visible spectroscopic studies have shown that Cu(II) mediated autoxidation of 4-methoxy-m-phenylenediamine and SOD accelerated the autoxidation. On the other hand, non-carcinogenic m-phenylenediamine did not cause clear DNA damage and significant autoxidation even in the presence of Cu(II). These results suggest that carcinogenicity of m-phenylenediamines is associated with ability to cause oxidative DNA damage rather than bacterial mutagenicity.
authors.affiliation: Department of Hygiene, Mie University School of Medicine, Tsu, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Murata
authors.forename: Y
authors.initials: Y
authors.lastname: Hiraku
authors.forename: N
authors.initials: N
authors.lastname: Yamashita
authors.forename: S
authors.initials: S
authors.lastname: Oikawa
authors.forename: S
authors.initials: S
authors.lastname: Kawanishi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D002273:Carcinogens / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003300:Copper / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D004563:Electrochemistry / Q000295:instrumentation / Q000379:methods; D016166:Free Radical Scavengers / Q000494:pharmacology; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D010618:Phenanthrolines / Q000494:pharmacology; D010655:Phenylenediamines / Q000633:toxicity*; D010761:Phosphorus Radioisotopes; D017382:Reactive Oxygen Species / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002273:Carcinogens; D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D010618:Phenanthrolines; D010655:Phenylenediamines; D010761:Phosphorus Radioisotopes; D017382:Reactive Oxygen Species; D003300:Copper; C007294:4-methoxy-3-phenylenediamine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C002478:bathocuproine; D003849:Deoxyguanosine; C008381:3-phenylenediamine