In vitro photogenotoxic activity of clinafloxacin: A paradigm predicting photocarcinogenicity

Fluoroquinolone antiinfective drugs exhibit phototoxic, photogenotoxic, and photocarcinogenic activities in experimental systems which may be interrel ated. Clinafloxacin (CLX), a new fluoroquinolone, is a potent antiinfective agent being developed for use in life-threatening infections. While this d rug has previously been demonstrated to be phototoxic, this report evaluate d the photogenotoxic and photocarcinogenic potential of CLX. When Skh-1 mic e were administered CLX in the presence of ultraviolet light (UVA) at the m aximum tolerated dose expected for a photocarcinogenicity bioassay, inducti on of DNA strand breakage was noted in keratinocytes isolated from these an imals. When compared with other well-studied fluoroquinolones in vitro, CLX and Lomefloxacin (LMX) were equally effective in producing chromosome dama ge 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 i n hydroxyl radical formation. However, coincubation of CHO cells with CLX a nd various antioxidants markedly reduced hydroxyl radical formation, but in hibited photogenotoxicity only to a limited extent. Thus, while reactive ox ygen species contribute to the photogenotoxic activity of CLX, other factor s may be involved. Since CLX exhibits both phototoxic and photogenotoxic ac tivity, we predict that CLX would be photocarcinogenic in vivo. The present study suggests that under conditions of human exposure, the potential risk for CLX-induced photocarcinogenicity is small. (C) 1999 Academic Press.