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: F Chen, M Murata, Y Hiraku, N Yamashita, S Oikawa, S Kawanishi
• Journal: Free radical research (Free Radic Res) Vol. 29 Issue 3 Pg. 197-205 (Sep 1998) ISSN: 1071-5762 [Print] England
• PMID: 9802551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Cytochrome c Group
• Free Radical Scavengers
• Phenanthrolines
• Phenylenediamines
• Phosphorus Radioisotopes
• Reactive Oxygen Species
• Copper
• 4-methoxy-3-phenylenediamine
• 8-Hydroxy-2'-Deoxyguanosine
• DNA
• bathocuproine
• Deoxyguanosine
• 3-phenylenediamine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Carcinogens (toxicity)
• Chromatography, High Pressure Liquid (methods)
• Copper (pharmacology)
• Cytochrome c Group (metabolism)
• DNA (metabolism)
• DNA Damage (drug effects)
• Deoxyguanosine (analogs & derivatives, analysis, metabolism)
• Electrochemistry (instrumentation, methods)
• Free Radical Scavengers (pharmacology)
• Genes, p53
• Genes, ras
• Humans
• Phenanthrolines (pharmacology)
• Phenylenediamines (toxicity)
• Phosphorus Radioisotopes
• Reactive Oxygen Species (metabolism)
• Spectrophotometry, Ultraviolet