Brown R F
Mutat Res. 1980 Mar;77(3):251-8. doi: 10.1016/0165-1218(80)90058-0.
Chlorpropamide, an oral hypoglycemic agent, was tested for effects on excision repair and postreplication repair of ultraviolet (UV) damage of DNA in CHO-K1 cells. The technique used to measure excision repair involved isopycnic centrifugation of density- and isotopically-labeled DNA. Alkaline sucrose gradient sedimentation was used to monitor postreplication repair. Administration of chlorpropamide at 250 and 1000 microgram/ml after exposure of cultures to 254-nm UV reduced excision repair to 79 and 67%, resp., of control. Post-irradiation treatment with the drug at 1000 microgram/ml inhibited the postreplication gap-filling mechanism almost as effectively as did 2 mM caffeine. The hypoglycemic agent was also found to reduce UV cell survival but did not appear to alter the rate of semiconservative replication. These results suggest that chlorpropamide inhibition of repair processes may potentiate the effects of known mutagenic hazards and may also be responsible for the increased incidence of chromosome aberrations in patients treated with the drug.
口服降糖药氯磺丙脲，在CHO-K1细胞中被测试对紫外线（UV）损伤DNA的切除修复和复制后修复的影响。用于测量切除修复的技术涉及对密度和同位素标记的DNA进行等密度离心。碱性蔗糖梯度沉降用于监测复制后修复。在培养物暴露于254纳米紫外线后，以250和1000微克/毫升的浓度施用氯磺丙脲，切除修复分别降至对照的79%和67%。用1000微克/毫升的药物进行辐照后处理，对复制后缺口填补机制的抑制效果几乎与2毫摩尔咖啡因相同。还发现这种降糖药会降低UV照射后的细胞存活率，但似乎不会改变半保留复制的速率。这些结果表明，氯磺丙脲对修复过程的抑制可能会增强已知诱变危害的影响，也可能是使用该药物治疗的患者染色体畸变发生率增加的原因。
