Repair of oxidative DNA base lesions induced by fluorescent light is defective in xeroderma pigmentosum group A cells.
Fluorescent light (FL) has been shown to generate free radicals within cells, however, the specific chemical nature of DNA damage induced by FL has not previously been determined. Using gas chromatography/isotope dilution mass spectrometry, we have detected induction of the oxidative DNA lesions 5-hydroxycytosine (5-OH-Cyt), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) and 4, 6-diamino-5-formamidopyrimidine (FapyAde) in cultured cells irradiated with FL. We followed the repair of these lesions in normal and xeroderma pigmentosum group A (XP-A) cells. 5-OH-Cyt and FapyGua were repaired efficiently in normal cells within 6 h following FL exposure. XP-A cells were unable to repair these oxidative DNA base lesions. Additionally, to compare the repair of oxidative lesions induced by various sources, in vitro repair studies were performed using plasmid DNA damaged by FL, gamma-irradiation or OsO(4)treatment. Whole cell extracts from normal cells repaired damaged substrates efficiently, whereas there was little repair in XP-A extracts. Our data demon-strate defective repair of oxidative DNA base lesions in XP-A cells in vivo and in vitro.
Lipinski
L J
LJ
Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Hoehr
N
N
Mazur
S J
SJ
Dianov
G L
GL
Sentürker
S
S
Dizdaroglu
M
M
Bohr
V A
VA
D002478:Cells, Cultured; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000528:radiation effects; D004247:DNA / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D043382:DNA-Formamidopyrimidine Glycosylase; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000378:metabolism; D029968:Escherichia coli Proteins; D005453:Fluorescence; D005720:Gamma Rays; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008214:Lymphocytes; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009993:Osmium Tetroxide / Q000378:metabolism; D010084:Oxidation-Reduction; D010957:Plasmids / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D011743:Pyrimidines / Q000378:metabolism / Q000528:radiation effects; D013997:Time Factors; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000473:pathology
D029968:Escherichia coli Proteins; D011743:Pyrimidines; C071023:2,6-diamino-4-hydroxy-5-formamidopyrimidine; C039544:4,6-diamino-5-N-formamidopyrimidine; C017400:5-hydroxycytosine; D003596:Cytosine; D004247:DNA; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D009993:Osmium Tetroxide