FLUOROQUINOLONE ANTIBACTERIALS ENHANCE UVA-INDUCED SKIN TUMORS

Fluoroquinolone antibacterials are known to be phototoxic, both in viv o and in vitro. The action spectrum for the phototoxicity of the quino lones lies mainly in the UVA region. During studies of systemic drug p hototoxicity, Johnson et al. (Dundee) induced dose-dependent phototoxi city in Swiss albino mice, and severe phototoxic reactions were follow ed by the development of skin tumors. The present study was designed t o compare the ability of several quinolones to produce photobiologic e ffects following chronic, subphototoxic UVA radiation. To compare the activities of different quinolones (lomefloxacin, fleroxacin, ciproflo xacin, ofloxacin and nalidixic acid), doses that result in similar pla sma and skin levels of drug were administered by gavage to slightly pi gmented Skh-1 hairless mice for up to 78 weeks. 8-Methoxypsoralen (8-M OP) was used as a positive control, and unirradiated, drug-treated and irradiated and unirradiated drug-free controls were also used. No sig ns of phototoxicity were seen, except for minimal-to-slight erythema a nd swelling of the skin in animals of the lomefloxacin-UVA group. Skin tumors (1 mm in diameter or larger) were observed in all the irradiat ed groups and the incidence was increased in all the groups treated wi th the test articles. The cumulative tumor prevalence was accelerated, the median latent periods were shortened and tumor onset was signific antly enhanced by 8-MOP plus UVA, lomefloxacin plus UVA and fleroxacin plus UVA, as compared with vehicle plus UVA-exposed animals. The majo rity of skin tumors (with the exception of lomefloxacin and 8-MOP) wer e benign. The majority of squamous cell carcinomas in the lomefloxacin group were of a histologic type different from those previously repor ted in UVA-exposed animals. Thus, all the fluoroquinolone antibiotics studied have the capability of enhancing UVA-induced phototumorigenesi s, but only lomefloxacin caused the development of cystic squamous cel l carcinomas in the majority of treated animals. (C) 1997 Elsevier Sci ence S.A.