Kersten B, Zhang J, Brendler-Schwaab S Y, Kasper P, Müller L
Federal Institute for Drugs and Medical Devices, Seestrasse 10, D-13353, Berlin, Germany.
Mutat Res. 1999 Sep 15;445(1):55-71. doi: 10.1016/s1383-5718(99)00143-6.
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.
近期有关氟喹诺酮类抗菌药物光化学致癌性和光化学基因毒性的报告，使人们越来越意识到需要一种标准方法来检测光化学基因毒性。在本研究中，使用V79细胞的微核试验被应用于光基因毒性检测。使用不同UVA/UVB关系的结果使我们能够确定一种合适的照射方案，用于激活不同种类的光敏剂。使用该方案，已确定8-甲氧基补骨脂素以及氟喹诺酮类药物洛美沙星、格帕沙星和Bay Y 3118在光化学激活后会导致微核形成和毒性。在所测试的吩噻嗪类药物中，氯丙嗪和2-氯吩噻嗪在两个终点均呈阳性，而三氟丙嗪在存在强光毒性的情况下仅具有轻微的光断裂作用。在所测试的其他潜在人体光敏剂（土霉素、强力霉素、甲硝唑、大黄素、金丝桃素、灰黄霉素）中，只有金丝桃素具有轻微的光基因毒性。观察到强力霉素和大黄素在无光化学基因毒性的情况下具有光化学毒性。使用所描述的检测系统，可以足够可靠地同时测定光化学毒性和光化学基因毒性。
