Brendler-Schwaab Susanne, Czich Andreas, Epe Bernd, Gocke Elmar, Kaina Bernd, Müller Lutz, Pollet Dieter, Utesch Dietmar
Toxicology, Bayer AG, D-42096 Wuppertal, Germany.
Mutat Res. 2004 Jan;566(1):65-91. doi: 10.1016/s1383-5742(03)00052-8.
In recent years, assessing the photogenotoxic potential of a compound became an issue for certain drugs and cosmetical products. Therefore, existing methods performed according to international guidelines (e.g. OECD guidelines) were adapted to the use of concurrent UV-visible (UV-Vis) light irradiation for the assessment of photomutagenicity/photogenotoxicity. In this review, photobiological bases of the processes occurring in the cell after irradiation with UV- and/or visible (vis)-light as well as a compilation of testing methods is presented. Methods comprise cell free investigations on naked DNA and in vitro methods, such as the photo-Ames test, the photo-HPRT/photo-mouse lymphoma assay (MLA), the photo-micronucleus test (MNT), the photo-chromosomal aberration test (CA) and the photo-Comet assay. A compilation of the currently available international literature of compounds tested on photogenotoxicity is given for each method. The state of the art of photogenotoxicity testing as well as the rational for testing are outlined in relation to the recommendations reached in expert working groups at different international meetings and to regulatory guidance papers. Finally, photogenotoxicity testing as predictor of photocarcinogenicity and in the light of risk assessment is discussed.
近年来,评估化合物的光遗传毒性潜力已成为某些药物和化妆品的一个问题。因此,根据国际指南(如经合组织指南)执行的现有方法被调整用于同时使用紫外可见(UV-Vis)光照射来评估光致突变性/光遗传毒性。在本综述中,介绍了细胞在紫外光和/或可见光照射后发生的过程的光生物学基础以及测试方法的汇总。方法包括对裸露DNA的无细胞研究和体外方法,如光致突变试验、光次黄嘌呤-鸟嘌呤磷酸核糖转移酶/光小鼠淋巴瘤试验(MLA)、光微核试验(MNT)、光染色体畸变试验(CA)和光彗星试验。针对每种方法给出了目前关于化合物光遗传毒性测试的国际文献汇总。光遗传毒性测试的现状以及测试的原理根据不同国际会议专家工作组达成的建议和监管指导文件进行了概述。最后,讨论了光遗传毒性测试作为光致癌性预测指标以及在风险评估方面的情况。