Proposed mechanism for the photodynamic generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine produced in cultured cells by exposure to lomefloxacin

Mutat Res. 1997 Nov 19;381(1):117-29. doi: 10.1016/s0027-5107(97)00159-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Anti-Infective Agents*
  • Antioxidants / pharmacology*
  • Butylated Hydroxyanisole / pharmacology
  • Cells, Cultured
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / chemistry
  • Deoxyguanosine / metabolism
  • Fluoroquinolones*
  • Liver / cytology
  • Liver / drug effects
  • Liver / radiation effects
  • Mannitol / pharmacology
  • Photosensitizing Agents / pharmacology*
  • Quinolones / pharmacology*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Sodium Azide / pharmacology
  • Ultraviolet Rays
  • Vitamin E / pharmacology

Substances

  • Anti-Infective Agents
  • Antioxidants
  • Fluoroquinolones
  • Photosensitizing Agents
  • Quinolones
  • Reactive Oxygen Species
  • Vitamin E
  • Butylated Hydroxyanisole
  • Mannitol
  • 8-Hydroxy-2'-Deoxyguanosine
  • Sodium Azide
  • Deoxyguanosine
  • lomefloxacin