Link C J, Evans M K, Cook J A, Muldoon R, Stevnsner T, Bohr V A
Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Carcinogenesis. 1995 May;16(5):1149-55. doi: 10.1093/carcin/16.5.1149.
We have studied the effect of caffeine on gene- and strand-specific DNA repair after exposure of Chinese hamster ovary cells and human xeroderma pigmentosum complementation group C (XPC) cells to ultraviolet irradiation (UV). In hamster cells, caffeine inhibited the repair of cyclobutane dimers (CPDs) in the dihydrofolate reductase (DHFR) gene by up to 66% after 8 h of repair incubation. This effect was dose-dependent, with more inhibition at 10 than at 1.5 mM caffeine. The inhibition was due to decreased repair in the transcribed strand of the hamster DHFR gene. This decrease in repair of CPDs in the DHFR gene correlated with an enhancement of UV-induced cell killing by caffeine. DNA repair was also measured in the overall genome by repair-replication analysis. In hamster cells, caffeine caused a modest enhancement of repair. Caffeine did not produce a significant effect on cell cycle progression up to 8 h after UV irradiation, but it caused a distinct block in early S phase during the 24 h post-irradiation period. In XPC cells, 10 mM caffeine inhibited the removal of CPDs from the transcribed strand of the DHFR gene by 92%. The removal of all photoproducts from the overall genome was inhibited by 26% in these cells. Since the residual repair in XPC cells is thought to occur in active genomic regions, we propose that caffeine preferentially inhibits gene-specific repair.
我们研究了咖啡因对中国仓鼠卵巢细胞和人类着色性干皮病互补组C（XPC）细胞暴露于紫外线照射（UV）后基因特异性和链特异性DNA修复的影响。在仓鼠细胞中，修复孵育8小时后，咖啡因抑制二氢叶酸还原酶（DHFR）基因中环丁烷二聚体（CPD）的修复高达66%。这种作用呈剂量依赖性，10 mM咖啡因的抑制作用比1.5 mM咖啡因更强。这种抑制是由于仓鼠DHFR基因转录链中的修复减少。DHFR基因中CPD修复的减少与咖啡因增强紫外线诱导的细胞杀伤作用相关。还通过修复复制分析在整个基因组中测量了DNA修复。在仓鼠细胞中，咖啡因使修复略有增强。在紫外线照射后长达8小时内，咖啡因对细胞周期进程没有显著影响，但在照射后24小时内，它在早期S期造成明显阻滞。在XPC细胞中，10 mM咖啡因抑制从DHFR基因转录链中去除CPD的效率达92%。在这些细胞中，从整个基因组中去除所有光产物的效率被抑制了26%。由于XPC细胞中的残余修复被认为发生在活跃的基因组区域，我们提出咖啡因优先抑制基因特异性修复。
