The application of the micronucleus test in Chinese hamster V79 cells to detect drug-induced photogenotoxicity.
Recent reports on the photochemical carcinogenicity and photochemical genotoxicity of fluoroquinolone antibacterials led to an increasing awareness for the need of a standard approach to test for photochemical genotoxicity. In this study the micronucleus test using V79 cells was adapted to photogenotoxicity testing. Results of using different UVA/UVB relationships enabled us to identify a suitable irradiation regimen for the activation of different kinds of photosensitizers. Using this regimen, 8-methoxypsoralen and the fluoroquinolones lomefloxacin, grepafloxacin and Bay Y 3118 were identified to cause micronuclei and toxicity upon photochemical activation. Among the phenothiazines tested, chlorpromazine and 2-chlorophenothiazine, were positive for both endpoints, whereas triflupromazine was only slightly photoclastogenic in the presence of strong phototoxicity. Among the other potential human photosensitizers tested (oxytetracycline, doxycycline, metronidazole, emodin, hypericin, griseofulvin), only hypericin was slightly photogenotoxic. Photochemical toxicity in the absence of photochemical genotoxicity was noted for doxycycline and emodin. With the assay system described, it is possible to determine photochemical toxicity and photochemical genotoxicity concomitantly with sufficient reliability.
Kersten
B
B
Federal Institute for Drugs and Medical Devices, Seestrasse 10, D-13353, Berlin, Germany. b.kersten@bfarm.de
Zhang
J
J
Brendler-Schwaab
S Y
SY
Kasper
P
P
Müller
L
L
D000818:Animals; D000873:Anthracenes; D000890:Anti-Infective Agents / Q000633:toxicity; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004642:Emodin / Q000633:toxicity; D024841:Fluoroquinolones; D006118:Griseofulvin / Q000633:toxicity; D008730:Methoxsalen / Q000633:toxicity; D008795:Metronidazole / Q000633:toxicity; D015162:Micronucleus Tests; D010569:Perylene / Q000031:analogs & derivatives / Q000633:toxicity; D010640:Phenothiazines / Q000633:toxicity; D017319:Photosensitizing Agents / Q000633:toxicity; D013754:Tetracyclines / Q000633:toxicity; D014466:Ultraviolet Rays
D000873:Anthracenes; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010640:Phenothiazines; D017319:Photosensitizing Agents; D013754:Tetracyclines; D008795:Metronidazole; D006118:Griseofulvin; D010569:Perylene; C004965:hypericin; D004247:DNA; D004642:Emodin; D008730:Methoxsalen