title: Oxidative DNA damage induced by hair dye components ortho-phenylenediamines and the enhancement by superoxide dismutase.
abstract: There is an association between occupational exposure to hair dyes and incidence of cancers. Permanent oxidant hair dyes are consisted of many chemical components including ortho-phenylenediamines. To clarify the mechanism of carcinogenesis by hair dyes, we examined DNA damage induced by mutagenic ortho-phenylenediamine (o-PD) and its derivatives, 4-chloro-ortho-phenylenediamine (Cl-PD) and 4-nitro-ortho-phenylenediamine (NO(2)-PD), using (32)P-labeled DNA fragments obtained from the human p16 and the p53 tumor suppressor gene. We also measured the content of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of oxidative DNA damage, in calf thymus DNA with an electrochemical detector coupled to a high performance liquid chromatograph. Carcinogenic o-PD and Cl-PD caused Cu(II)-mediated DNA damage, including 8-oxodG formation, and antioxidant enzyme superoxide dismutase (SOD) enhanced DNA damage. o-PD and Cl-PD caused piperidine-labile and formamidopyrimidine-DNA glycosylase-sensitive lesions at cytosine and guanine residues respectively in the 5'-ACG-3' sequence, complementary to codon 273, a well-known hotspot of the human p53 tumor suppressor gene. UV-vis spectroscopic studies showed that the spectral change of o-PD and Cl-PD required Cu(II), and addition of SOD enhanced it. This suggested that SOD enhanced the rate of Cu(II)-mediated autoxidation of o-PD and Cl-PD, leading to enhancement of DNA damage. On the other hand, mutagenic but non-carcinogenic NO(2)-PD induced no DNA damage. These results suggest that carcinogenicity of ortho-phenylenediamines is associated with ability to cause oxidative DNA damage rather than bacterial mutagenicity.
authors.affiliation: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Murata
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nishimura
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Shosuke
authors.initials: S
authors.lastname: Kawanishi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002417:Cattle; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D018920:Coculture Techniques; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D019942:Genes, p16; D016158:Genes, p53; D006202:Hair Dyes / Q000737:chemistry*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D010084:Oxidation-Reduction; D010655:Phenylenediamines / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D006202:Hair Dyes; D010655:Phenylenediamines; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; D013482:Superoxide Dismutase; D003849:Deoxyguanosine