Skare J A, Wong T K
Cancer Lett. 1985 Mar;26(2):191-200. doi: 10.1016/0304-3835(85)90026-6.
The ability of sodium saccharin (NaS) to inhibit the repair of DNA damaged by UV irradiation was examined in cultured WI-38 human diploid fibroblasts. Cesium chloride density gradient ultracentrifugation was used to measure DNA repair and DNA replication. NaS (10-10,000 micrograms/ml) did not specifically inhibit UV light-induced DNA repair. At doses of NaS (1785 and 10,000 micrograms/ml) that caused a 62-67% inhibition of semiconservative DNA replication, there was little or no inhibition of DNA repair synthesis. In cell cultures not exposed to UV irradiation, NaS failed to induce DNA repair. RNA synthesis and protein synthesis were unaffected by NaS at all doses tested. The inhibition of semiconservative DNA replication at higher doses of NaS may be a manifestation of cytotoxicity. In contrast to results with NaS, WI-38 cells were very sensitive to DNA repair inhibition by the well-studied inhibitor quinacrine-HCl. These results do not support mechanisms of saccharin-induced tumorigenesis involving either direct induction of DNA damage or inhibition of the repair of DNA damage caused by other agents.
在培养的WI-38人二倍体成纤维细胞中检测了糖精钠（NaS）抑制紫外线照射损伤DNA修复的能力。采用氯化铯密度梯度超速离心法测定DNA修复和DNA复制。NaS（10 - 10000微克/毫升）并未特异性抑制紫外线诱导的DNA修复。在导致半保留DNA复制抑制62 - 67%的NaS剂量（1785和10000微克/毫升）下，DNA修复合成几乎没有受到抑制。在未暴露于紫外线照射的细胞培养物中，NaS未能诱导DNA修复。在所有测试剂量下，RNA合成和蛋白质合成均不受NaS影响。较高剂量NaS对半保留DNA复制的抑制可能是细胞毒性的一种表现。与NaS的结果相反，WI-38细胞对经过充分研究的抑制剂盐酸阿的平抑制DNA修复非常敏感。这些结果不支持糖精诱导肿瘤发生的机制涉及直接诱导DNA损伤或抑制其他因素导致的DNA损伤修复。
