Keyse S M, Tyrrell R M
Carcinogenesis. 1985 Aug;6(8):1231-3. doi: 10.1093/carcin/6.8.1231.
The effects of novobiocin and nalidixic acid on the specific toxicity of aphidicolin towards u.v. irradiated arrested (nondividing) human skin fibroblasts have been determined. Contrary to the result expected if either drug were causing inhibition of excision repair at a pre-incision step the sector of toxicity due to a combined treatment of 300 micrograms ml-1 nalidixic acid and 1.0 micrograms ml-1 aphidicolin is unchanged when compared with that due to treatment with 1.0 micrograms ml-1 aphidicolin alone, while that for 150 micrograms ml-1 novobiocin + 1.0 micrograms ml-1 aphidicolin was slightly increased. In parallel measurements of the inhibition of u.v.-induced DNA repair synthesis in arrested fibroblasts by these drugs, 150 micrograms ml-1 novobiocin inhibited repair synthesis by approximately 60% over the fluence range employed. Nalidixic acid at a concentration of 300 micrograms ml-1 caused no detectable inhibition of repair synthesis. We conclude that the mode of action of novobiocin in the inhibition of DNA excision repair is not via the inhibition of a pre-incision step and the data do not support the hypothesis that a type II topoisomerase mediated change in DNA supercoiling is an essential early step in excision repair of u.v.-induced damage.
已测定新生霉素和萘啶酸对阿非科林针对紫外线照射后停滞（不分裂）的人皮肤成纤维细胞的特异性毒性的影响。与预期结果相反，如果这两种药物中的任何一种在切口前步骤导致切除修复受到抑制，那么与单独使用1.0微克/毫升阿非科林相比，联合使用300微克/毫升萘啶酸和1.0微克/毫升阿非科林时的毒性区域没有变化，而150微克/毫升新生霉素 + 1.0微克/毫升阿非科林的毒性区域略有增加。在对这些药物对停滞的成纤维细胞中紫外线诱导的DNA修复合成的抑制进行的平行测量中，在所用的通量范围内，150微克/毫升新生霉素抑制修复合成约60%。浓度为300微克/毫升的萘啶酸未引起可检测到的修复合成抑制。我们得出结论，新生霉素抑制DNA切除修复的作用方式不是通过抑制切口前步骤，并且这些数据不支持II型拓扑异构酶介导的DNA超螺旋变化是紫外线诱导损伤切除修复中必不可少的早期步骤这一假设。
