Sequence-specific DNA damage induced by ultraviolet A-irradiated folic acid via its photolysis product.
DNA damage mediated by photosensitizers participates in solar carcinogenesis. Fluorescence measurement and high-performance liquid chromatography analysis demonstrated that photoirradiated folic acid, one of the photosensitizers in cells, generates pterine-6-carboxylic acid (PCA). Experiments using 32P-labeled DNA fragments obtained from a human gene showed that ultraviolet A-irradiated folic acid or PCA caused DNA cleavage specifically at consecutive G residues in double-stranded DNA after Escherichia coli formamidopyrimidine-DNA glycosylase or piperidine treatment. The amount of 8-oxo-7,8-dihydro-2(')-deoxyguanosine formed through this DNA photoreaction in double-stranded DNA exceeded that in single-stranded DNA. Kinetic studies suggested that DNA damage is caused mainly by photoexcited PCA generated from folic acid rather than by folic acid itself. In conclusion, photoirradiated folic acid generates PCA, which induces DNA photooxidation specifically at consecutive G residues through electron transfer. Excess intake of folic acid supplements may increase a risk of skin cancer by solar ultraviolet light.
Hirakawa
Kazutaka
K
Radioisotope Center, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 514-8507, Japan.
Suzuki
Hiroyuki
H
Oikawa
Shinji
S
Kawanishi
Shosuke
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008027:Light; D008956:Models, Chemical; D017434:Protein Structure, Tertiary; D014466:Ultraviolet Rays
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D005492:Folic Acid; D003849:Deoxyguanosine