Photosensitized DNA damage induced by NADH: site specificity and mechanism.
Increasing evidence reveals the carcinogenicity of UVA radiation. We demonstrated that UVA-irradiated NADH induced damage to (32)P-labeled DNA fragments obtained from the p53 gene in the presence of Cu(II). Formamidopyrimidine glycosylase (Fpg)-sensitive lesions were formed at guanine residues, whereas piperidine-labile lesions occurred frequently at thymine residues. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), upon UVA exposure in the presence of Cu(II), increased depending on NADH concentration. Catalase and bathocuproine, a Cu(I)-specific chelator, inhibited the DNA damage, suggesting the involvement of reactive species derived from H(2)O(2) and Cu(I). UVA-irradiated riboflavin induced DNA cleavage through electron transfer at 5' guanine of the 5'-GG-3' sequence with both Fpg and piperidine treatments; Fpg induced less cleavage at the guanine residues than piperidine. These results imply that NADH may participate as an endogenous photosensitizer in UVA carcinogenesis via H(2)O(2) generation, producing metal-mediated mutagenic lesions such as 8-oxodG.
Ito
Kimiko
K
Department of Life Science, Tsu City College, Tsu, Mie 514-0112, Japan.
Hiraku
Yusuke
Y
Kawanishi
Shosuke
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002417:Cattle; D004249:DNA Damage; D053938:DNA Fragmentation; D043382:DNA-Formamidopyrimidine Glycosylase / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D016158:Genes, p53; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008027:Light; D009243:NAD / Q000737:chemistry*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D012256:Riboflavin / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
D017319:Photosensitizing Agents; D016159:Tumor Suppressor Protein p53; D009243:NAD; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine; D012256:Riboflavin