Inhibition by singlet oxygen quenchers of oxidative damage to DNA produced in cultured cells by exposure to a quinolone antibiotic and ultraviolet A irradiation.
The photogenotoxicity mechanism of quinolone antibiotics was investigated by measuring oxidative DNA damage in lomefloxacin- and UVA-exposed cultured liver-derived cells. The combination of lomefloxacin and UVA irradiation produced a dose-dependent increase in 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) in cell DNA. This DNA damage was substantially inhibited by co-incubation with sodium azide (NaN3) or 2,2,6,6-tetramethyl-4-piperadone (TMP), chemicals that specifically quench singlet oxygen. No significant reduction of 8-oxo-dG formation was produced by N-t-butyl-alpha-phenylnitrone (TBP) or alpha-tocopherol, which primarily scavenge hydroxyl radicals. We conclude that the photodynamic generation of 8-oxo-dG by quinolones is mediated, at least in part, by singlet oxygen.
Verna
L K
LK
American Health Foundation, Valhalla, New York, USA.
Chen
D
D
Schluter
G
G
Williams
G M
GM
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D024841:Fluoroquinolones; D010100:Oxygen / Q000037:antagonists & inhibitors*; D010777:Photochemistry; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species; D026082:Singlet Oxygen; D014466:Ultraviolet Rays
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D017382:Reactive Oxygen Species; D026082:Singlet Oxygen; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; C053091:lomefloxacin; D010100:Oxygen