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 cell s, however, the specific chemical nature of DNA damage induced by FL has no t previously been determined. Using gas chromatography/isotope dilution mas s spectrometry, we have detected induction of the oxidative DNA lesions 5-h ydroxycytosine (5-OH-Cyt), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fap yGua) and 4,6-diamino-5-formamidopyrimidine (FapyAde) in cultured cells irr adiated with FL, We followed the repair of these lesions in normal and xero derma 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 we re unable to repair these oxidative DNA base lesions. Additionally, to comp are the repair of oxidative lesions induced by various sources, in vitro re pair studies were performed using plasmid DNA damaged by FL, gamma-irradiat ion or OsO4 treatment. Whole cell extracts from normal cells repaired damag ed substrates efficiently, whereas there was little repair in XP-A extracts , Our data demonstrate defective repair of oxidative DNA base lesions in XP -A cells in vivo and in vitro.