Photochemical mutagenicity of phototoxic and photochemically carcinogenic fluoroquinolones in comparison with the photostable moxifloxacin.
Photochemical mutagenicity of phototoxic and photochemically carcinogenic fluoroquinolones in comparison with the photostable moxifloxacin.
复制标题
光毒性和光化学致癌性氟喹诺酮类药物与光稳定性莫西沙星相比的光化学致突变性。
DOI：
10.1007/s002040000162
复制
发表时间：
2000
影响因子：
6.1
通讯作者：
Williams,GM
中科院分区：
文献类型：
--
作者：
Jeffrey,AM;Shao,L;Brendler-Schwaab,SY;Schlüter,G;Williams,GM
某些氟喹诺酮（FQ）抗生素，显示临床光毒性和实验光化学致癌性已被发现与紫外线-A（UVA）辐射相互作用，在培养的细胞和分离的DNA中产生氧化DNA损伤。为了研究哺乳动物细胞中DNA氧化损伤的生物学后果，在V79细胞中研究了两种光活性FQs，洛美沙星和Bay y3118的光化学致突变性，并与光稳定的氟喹诺酮类药物进行了比较。洛美沙星和Bay y3118在UVA照射下对V79细胞具有光化学致突变性，分别使突变频率增加约8倍（400 µM，6000 J/m2）和10倍（50 µM，1000 J/m2），而曲库沙星（400 µM，9000 J/m2）未观察到光化学致突变性。我们认为，先前报道的洛美沙星和Bay y3118光化学产生氧化DNA损伤的能力，这是已知的致突变性，可能是光化学致突变性和光化学致癌性的基础。光稳定的阿替沙星似乎缺乏这样的性质。
Certain fluoroquinolone (FQ) antibiotics that show clinical phototoxicity and experimental photochemical carcinogenicity have been found to interact with ultraviolet-A (UVA) radiation to produce oxidative DNA damage in cultured cells and isolated DNA. To study the biological consequences of oxidative DNA damage in mammalian cells, the photochemical mutagenicity of two photoactive FQs, lomefloxacin and Bay y3118, was studied in V79 cells in comparison with that of the photostable moxifloxacin. Lomefloxacin and Bay y3118 were photochemically mutagenic to V79 cells with UVA irradiation, increasing the mutation frequency by about eightfold (400 µM, 6000 J/m2) and tenfold (50 µM, 1000 J/m2), respectively, whereas no photochemical mutagenicity was observed with moxifloxacin (400 µM, 9000 J/m2). We suggest that the previously reported ability of lomefloxacin and Bay y3118 to photochemically produce oxidative DNA damage, which is known to be mutagenic, may be the basis for the photochemical mutagenicity and the reported photochemical carcinogenicity. The photostable moxifloxacin appears to lack such properties.