Simon T M, Kunishima D H, Vibert G J, Lorber A
Cancer. 1979 Dec;44(6):1965. doi: 10.1002/1097-0142(197912)44:6<1965::aid-cncr2820440602>3.0.co;2-6.
Auranofin (AF), a recently introduced oral antirheumatic coordinated gold compound, was investigated for its antitumor potential. Due to certain similarities with the antitumor-coordinated compound, cis-Diamminedichloroplatinum II, we studied the effects of AF on cell proliferation. These studies included assessing DNA, RNA, and protein synthesis as measured by incorporation of 3H-thymidine, 3H-uridine, and 3H-leucine, respectively, into HeLa cells. AF was shown to exert a dose-dependent inhibition on DNA synthesis and to inhibit 3H-thymidine uptake more rapidly and persistently than 3H-uridine or 3H-leucine uptake at a gold concentration of 75--100 micrograms/dl. These three parameters were inhibited with a 24-hour exposure to 100 micrograms/dl. The inhibition of 3H-thymidine uptake in HeLa pretreated for 6 hours with 50 or 100 micrograms/dl of gold was found to be irreversible. No change in tracer uptake was observed in the acid-soluble pool or in the uptake of 3H-2-deoxy-D-glucose in these cells. Furthermore, HeLa cells demonstrated marked reductions in viability and oxygen uptake after exposure to AF. Dose-dependent surface morphological changes, e.g., blebbing, pitting, were noted in these cells after a brief treatment period. These results suggest this coordinated gold compount exerts a significant inhibitory effect on essential biological processes and functions.
金诺芬（AF）是一种最近推出的口服抗风湿配位金化合物，对其抗肿瘤潜力进行了研究。由于与抗肿瘤配位化合物顺二氯二氨铂II有某些相似之处，我们研究了AF对细胞增殖的影响。这些研究包括分别通过将3H-胸腺嘧啶核苷、3H-尿苷和3H-亮氨酸掺入HeLa细胞来评估DNA、RNA和蛋白质的合成。结果表明，在金浓度为75-100微克/分升时，AF对DNA合成具有剂量依赖性抑制作用，并且比3H-尿苷或3H-亮氨酸摄取更快速、持久地抑制3H-胸腺嘧啶核苷摄取。暴露于100微克/分升24小时可抑制这三个参数。发现用50或100微克/分升的金预处理6小时的HeLa细胞中3H-胸腺嘧啶核苷摄取的抑制是不可逆的。在这些细胞的酸溶性池中未观察到示踪剂摄取的变化，也未观察到3H-2-脱氧-D-葡萄糖摄取的变化。此外，HeLa细胞在暴露于AF后活力和氧摄取显著降低。在短暂处理期后，这些细胞中观察到剂量依赖性的表面形态变化，例如起泡、凹陷。这些结果表明这种配位金化合物对基本的生物学过程和功能具有显著的抑制作用。
