In VitroPhotogenotoxic Activity of Clinafloxacin: A Paradigm Predicting Photocarcinogenicity

Fluoroquinolone antiinfective drugs exhibit phototoxic, photogenotoxic, and photocarcinogenic activities in experimental systems which may be interrelated. Clinafloxacin (CLX), a new fluoroquinolone, is a potent antiinfective agent being developed for use in life-threatening infections. While this d...

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Published inToxicology and applied pharmacology Vol. 156; no. 3; pp. 222 - 230
Main Authors Bulera, S.J., Theiss, J.C., Festerling, T.A., de la Iglesia, F.A.
Format Journal Article
LanguageEnglish
Published Elsevier Inc 01.05.1999
Subjects
Ciprofloxacin
Clinafloxacin
fluoroquinolones
Lomefloxacin
photogenotoxicity
Clinafloxacin
fluoroquinolones
photogenotoxicity
Ciprofloxacin
Lomefloxacin
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Summary:Fluoroquinolone antiinfective drugs exhibit phototoxic, photogenotoxic, and photocarcinogenic activities in experimental systems which may be interrelated. Clinafloxacin (CLX), a new fluoroquinolone, is a potent antiinfective agent being developed for use in life-threatening infections. While this drug has previously been demonstrated to be phototoxic, this report evaluated the photogenotoxic and photocarcinogenic potential of CLX. When Skh-1 mice were administered CLX in the presence of ultraviolet light (UVA) at the maximum tolerated dose expected for a photocarcinogenicity bioassay, induction of DNA strand breakage was noted in keratinocytes isolated from these animals. When compared with other well-studied fluoroquinolonesin vitro,CLX and Lomefloxacin (LMX) were equally effective in producing chromosome damage and DNA strand breakage in Chinese hamster ovary (CHO) cells exposed to UVA. Treatment of CHO cells with CLX in the presence of UVA also resulted in hydroxyl radical formation. However, coincubation of CHO cells with CLX and various antioxidants markedly reduced hydroxyl radical formation, but inhibited photogenotoxicity only to a limited extent. Thus, while reactive oxygen species contribute to the photogenotoxic activity of CLX, other factors may be involved. Since CLX exhibits both phototoxic and photogenotoxic activity, we predict that CLX would be photocarcinogenicin vivo.The present study suggests that under conditions of human exposure, the potential risk for CLX-induced photocarcinogenicity is small.
ISSN:0041-008X
1096-0333
DOI:10.1006/taap.1999.8653