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DNA strand-breaking activities of quinolone antimicrobial agents under visible light irradiation
Y Iwamoto1, A Kurita, T Shimizu
1Department of Microbiology, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Abstract:
The DNA strand-breaking activities of 9 quinolones, widely used as antimicrobial agents and suspected to induce photo-dermatological disorders in humans, were examined under irradiation using standard domestic fluorescent lamps. Two quinolones, tosufloxacin and enoxacin, converted the supercoiled covalently closed circular plasmid DNA to the open circular form under visible light irradiation. The maximum of photodynamic single strand-breaking activity for tosufloxacin was found to be 12% at 50 microM and that of enoxacin was 33% at a concentration of 2 mM. The DNA strand-breaking activities of photoirradiated tosufloxacin and enoxacin were markedly inhibited by NaN3 but only partially by D-mannitol, superoxide dismutase (SOD) and catalase did not inhibit these activities. These results suggest that some quinolone antimicrobial agents can be activated by visible light and induce phototoxic DNA damage in various organisms. We should carefully investigate such phototoxic activities during the development of new quinolones to avoid producing phototoxic disorders in man.
Insights
Certain quinolone antimicrobials can cause DNA damage when exposed to visible light. This phototoxic DNA damage, observed with tosufloxacin and enoxacin, may contribute to photo-dermatological issues in humans.
Area of Science:
- Photochemistry
- Molecular Biology
- Dermatology
Background:
- Quinolones are widely used antimicrobial agents.
- Some quinolones are suspected to cause photo-dermatological disorders.
- DNA strand-breaking activity under light exposure is a concern.
Purpose of the Study:
- To investigate the DNA strand-breaking activities of nine quinolones under visible light irradiation.
- To identify specific quinolones that exhibit photodynamic DNA damage.
- To elucidate the mechanism of light-induced DNA damage by quinolones.
Main Methods:
- Irradiation of plasmid DNA with nine quinolones using standard domestic fluorescent lamps.
- Analysis of DNA structural changes (supercoiled to open circular form).
- Assessment of inhibition by scavengers like sodium azide, D-mannitol, superoxide dismutase, and catalase.
Main Results:
- Tosufloxacin and enoxacin induced DNA strand breaks under visible light.
- Photodynamic single strand-breaking activity was observed for both compounds.
- Inhibition studies suggested a role for reactive oxygen species, but not solely superoxide or hydrogen peroxide.
Conclusions:
- Certain quinolone antimicrobial agents can be activated by visible light to cause phototoxic DNA damage.
- Tosufloxacin and enoxacin demonstrate this phototoxic potential.
- Further investigation of phototoxic activities is crucial during new quinolone development to prevent human phototoxic disorders.