Fluoroquinolone antibacterials enhance UVA-induced skin tumors.
Fluoroquinolone antibacterials are known to be phototoxic, both in vivo and in vitro. The action spectrum for the phototoxicity of the quinolones lies mainly in the UVA region. During studies of systemic drug phototoxicity, Johnson et al. (Dundee) induced dose-dependent phototoxicity in Swiss albino mice, and severe phototoxic reactions were followed by the development of skin tumors. The present study was designed to compare the ability of several quinolones to produce photobiologic effects following chronic, subphototoxic UVA radiation. To compare the activities of different quinolones (lomefloxacin, fleroxacin, ciprofloxacin, ofloxacin and nalidixic acid), doses that result in similar plasma and skin levels of drug were administered by gavage to slightly pigmented Skh-1 hairless mice for up to 78 weeks. 8-Methoxypsoralen (8-MOP) was used as a positive control, and unirradiated, drug-treated and irradiated and unirradiated drug-free controls were also used. No signs of phototoxicity were seen, except for minimal-to-slight erythema and swelling of the skin in animals of the lomefloxacin-UVA group. Skin tumors (1 mm in diameter or larger) were observed in all the irradiated groups and the incidence was increased in all the groups treated with the test articles. The cumulative tumor prevalence was accelerated, the median latent periods were shortened and tumor onset was significantly enhanced by 8-MOP plus UVA, lomefloxacin plus UVA and fleroxacin plus UVA, as compared with vehicle plus UVA-exposed animals. The majority of skin tumors (with the exception of lomefloxacin and 8-MOP) were benign. The majority of squamous cell carcinomas in the lomefloxacin group were of a histologic type different from those previously reported in UVA-exposed animals. Thus, all the fluoroquinolone antibiotics studied have the capability of enhancing UVA-induced phototumorigenesis, but only lomefloxacin caused the development of cystic squamous cell carcinomas in the majority of treated animals.
Klecak
G
G
Department of Toxicology, F. Hoffmann-La Roche AG, Basel, Switzerland.
Urbach
F
F
Urwyler
H
H
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D002939:Ciprofloxacin / Q000633:toxicity; D005260:Female; D016576:Fleroxacin / Q000633:toxicity*; D024841:Fluoroquinolones; D051379:Mice; D009268:Nalidixic Acid / Q000633:toxicity; D009381:Neoplasms, Radiation-Induced / Q000139:chemically induced*; D015242:Ofloxacin / Q000633:toxicity; D015363:Quinolones / Q000633:toxicity; D012878:Skin Neoplasms / Q000139:chemically induced*; D014466:Ultraviolet Rays
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D009268:Nalidixic Acid; D002939:Ciprofloxacin; D015242:Ofloxacin; C053091:lomefloxacin; D016576:Fleroxacin