Tyrrell R M
Carcinogenesis. 1983;4(3):327-9. doi: 10.1093/carcin/4.3.327.
Aphidicolin, a specific inhibitor of the eucaryotic alpha polymerase, has been employed to study the role of this enzyme in repair of potentially lethal damage (PLD) induced by far u.v. (254 nm) radiation in normal and repair defective primary human fibroblasts. There is strong concentration dependent specific toxicity to cells treated with a fluence of 6 Jm-2 of far-u.v. radiation and incubated with aphidicolin for 2 days over the concentration range 0.0025-2.5 micrograms/ml. A similar effect is seen with a xeroderma pigmentosum (XP) variant (excision proficient) strain but there is no specific toxicity to u.v. irradiated excision deficient XP cells of complementation group A. Inactivation of irradiated excision proficient fibroblasts is rapid over the first 6 h of aphidicolin (1 microgram/ml) treatment but the reaction takes 2 days or longer to complete depending on the u.v. dose. These results demonstrate that the apparent uncoupling of excision repair seen previously by other investigators prevents repair of PLD and is lethal to the cells.
放线菌素，一种真核α聚合酶的特异性抑制剂，已被用于研究该酶在正常和修复缺陷的原代人成纤维细胞中由远紫外线（254nm）辐射诱导的潜在致死性损伤（PLD）修复中的作用。在用6J/m²的远紫外线辐射处理并在0.0025 - 2.5微克/毫升的浓度范围内与放线菌素孵育2天的细胞中，存在强烈的浓度依赖性特异性毒性。在着色性干皮病（XP）变异型（切除 proficient）菌株中也观察到类似的效果，但对紫外线照射的互补组A的切除缺陷型XP细胞没有特异性毒性。在用放线菌素（1微克/毫升）处理的最初6小时内，受辐射的切除 proficient 成纤维细胞的失活很快，但根据紫外线剂量的不同，反应需要2天或更长时间才能完成。这些结果表明，其他研究者之前观察到的切除修复明显解偶联会阻止PLD的修复，并对细胞具有致死性。
