Site-specific hydroxylation at polyguanosine in double-stranded DNA by UVA radiation with nalidixic acid.
Nalidixic acid (NA) has been used for urinary tract infections and has been reported to be photocarcinogenic. We examined the mechanism of damage to 32P-labeled DNA fragments obtained from the human c-Ha-ras-1 proto-oncogene and the p53 tumor suppressor gene exposed to 365-nm UVA light in the presence of NA. NA plus UVA light caused damage to the double-stranded DNA fragment at consecutive guanine residues, whereas damage to the single-stranded DNA fragment was caused at single guanines and thymines. The formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine in native DNA exceeded that in denatured DNA at high NA concentrations. The ESR spin destruction method suggested that DNA damage was caused through electron transfer from guanine residues to photoexcited NA. On the basis of these findings, it is concluded that NA can cause skin cancer through DNA damage mediated by its photoactivation.
Hiraku
Y
Y
Department of Hygiene, Mie University School of Medicine, Mie, Tsu, 514-8507, Japan.
Ito
H
H
Kawanishi
S
S
D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004578:Electron Spin Resonance Spectroscopy; D016158:Genes, p53; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008969:Molecular Sequence Data; D009268:Nalidixic Acid / Q000494:pharmacology*; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000528:radiation effects; D011068:Poly G; D000090063:Proto-Oncogene Mas; D014466:Ultraviolet Rays
C000715470:MAS1 protein, human; D009838:Oligodeoxyribonucleotides; D000090063:Proto-Oncogene Mas; D011068:Poly G; D009268:Nalidixic Acid; D004247:DNA