Photo-chemically induced DNA effects in the comet assay with epidermal cells of SKH-1 mice after a single oral administration of different fluoroquinolones and 8-methoxypsoralen in combination with exposure to UVA.
Due to the need for in vivo photo-genotoxicity tests, the in vivo photo-comet assay was established in epidermal cells of the SKH-1 mouse. Groups of 10 male SKH-1 mice each were treated once orally with vehicle only, with three fluoroquinolones (25 mg/kg clinafloxacin, 20 mg/kg lomefloxacin, 200 mg/kg ciprofloxacin) or with 200mg/kg 8-methoxypsoralene (8-MOP). Thirty minutes after treatment half of the mice in each group were exposed to 23.8 J/cm2 UVA. Thereafter the mice were killed and their epidermal cells tested in the alkaline (pH >13) comet assay; at the same time after administration, compound-treated, non-irradiated mice were killed and analysed. A negative control group of ten male SKH-1 mice received the vehicle only; half of these animals were exposed to UVA, half were not. The comet tail lengths of epidermal cells of the mice were statistically significantly increased for all three fluoroquinolones (FQ) tested in combination with UV irradiation. Treatment with 8-methoxypsoralene+UV induced a significant reduction of comet tail length. Tail intensity and tail moment gave essentially the same results after combined exposure (compound+UV). Without irradiation, the tail lengths of controls and compound-treated mice were comparable under the conditions of this study. In contrast, tail intensity and tail moment were increased for all test compounds (including 8-MOP), without irradiation. Irradiated controls had a tail length comparable to non-irradiated controls, while tail intensity and tail moment were clearly increased in irradiated controls.


CONCLUSIONS
under the present experimental conditions the in vivo photo-comet assay is able to detect photo-chemically induced DNA strand breaks as well as photo-chemically induced DNA cross-links.
Wirnitzer
Uta
U
Bayer HealthCare AG, Pharma Center, Toxicology, Building 514, P.O. Box 101709, 42096 Wuppertal, Germany. uta.wirnitzer@bayerhealthcare.com
Gross-Tholl
Nicole
N
Herbold
Bernd
B
von Keutz
Eckhard
E
D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000633:toxicity; D020552:Comet Assay; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008730:Methoxsalen / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008812:Mice, Hairless; D015363:Quinolones / Q000008:administration & dosage / Q000633:toxicity; D014466:Ultraviolet Rays
D024841:Fluoroquinolones; D015363:Quinolones; D002939:Ciprofloxacin; C057477:clinafloxacin; D004247:DNA; C053091:lomefloxacin; D008730:Methoxsalen