Proposed mechanism for the photodynamic generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine produced in cultured cells by exposure to lomefloxacin.
In this study, lomefloxacin (LMX), a widely used quinolone antibiotic with a high frequency of clinical phototoxicity, was investigated by measuring the effects of several antioxidants on its ability to form of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in cultured adult rat liver cells after exposure to UVA. In the current study the observed DNA damage, reflected by the formation of 8-oxo-dG, was almost completely inhibited by co-incubation of LMX and cultured cells with sodium azide (NaN3) that specifically quenches singlet oxygen. Vitamin E (alpha-tocopherol), known to quench both superoxide and singlet oxygen, inhibited 8-oxo-dG formation by approximately 54%. Mannitol, a hydroxyl radical scavenger, inhibited 8-oxo-dG formation by 64%. Butylated hydroxyanisole (BHA), a scavenger of hydroxyl, peroxy and alkoxy radicals, showed no inhibition of 8-oxo-dG formation but in fact enhanced levels of 8-oxo-dG by 169%. The results of this study suggest that the mechanism for the photodynamic generation of 8-oxo-dG by LMX is mediated, at least in part, by both singlet oxygen and hydroxyl radical and involves both type I and type II photosensitization.
Rosen
J E
JE
Department of Pathology and Toxicology, American Health Foundation, Valhalla, NY 10595, USA.
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000890:Anti-Infective Agents; D000975:Antioxidants / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002478:Cells, Cultured; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D024841:Fluoroquinolones; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D008353:Mannitol / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D019810:Sodium Azide / Q000494:pharmacology; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000494:pharmacology
D000890:Anti-Infective Agents; D000975:Antioxidants; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D015363:Quinolones; D017382:Reactive Oxygen Species; D014810:Vitamin E; D002083:Butylated Hydroxyanisole; D008353:Mannitol; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019810:Sodium Azide; D003849:Deoxyguanosine; C053091:lomefloxacin