The phototumorigenic fluoroquinolone lomefloxacin photosensitizes pyrimidine dimer formation in human keratinocytes in vitro.
The fluoroquinolone antibiotic lomefloxacin is phototoxic, photogenotoxic, photomutagenic and photosensitizes tumorigenesis in mouse skin. We have used T4 endonuclease V to demonstrate that lomefloxacin photosensitizes pyrimidine dimer formation in a human keratinocyte line (HaCaT). A possible mechanism for this effect would be triplet-triplet energy transfer. However, there is indirect evidence that the lomefloxacin triplet yield is very low, making this reaction less likely. The finding that lomefloxacin photosensitizes production of highly mutagenic pyrimidine dimers correlates with its ability to initiate skin tumor formation in mice. Until the potential of other fluoroquinolones to photosensitize dimer formation is explored it may be unadvisable to prescribe these antibiotics to patients with defective DNA repair capacity (e.g. xeroderma pigmentosum).
Traynor
N J
NJ
Photobiology Unit, University of Dundee, Ninewells Hospital, UK. n.k.gibbs@dundee.ac.uk
Gibbs
N K
NK
D000890:Anti-Infective Agents / Q000633:toxicity*; D002461:Cell Line, Transformed; D004249:DNA Damage; D024841:Fluoroquinolones; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D017319:Photosensitizing Agents / Q000633:toxicity*; D011740:Pyrimidine Dimers / Q000096:biosynthesis*; D015363:Quinolones / Q000633:toxicity*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D011740:Pyrimidine Dimers; D015363:Quinolones; C053091:lomefloxacin