Cohen J D, Robins H I
University of Wisconsin Clinical Cancer Center, Madison 53792.
Invest New Drugs. 1990 May;8(2):137-42. doi: 10.1007/BF00177247.
Diethyldithiocarbamate (DDTC) and other dithiocarbamates are currently receiving attention as potential adjuncts to traditional chemotherapy. In vitro studies with rodent cancer cell lines have consistently shown that DDTC concentrations of 0.1-1.0 micrograms/ml are highly cytotoxic. Paradoxically, however, concentrations of 10-100 micrograms/ml have been significantly less toxic. In the present study, such a 'biphasic' pattern was reproduced when 3 rodent cell lines were exposed for 1 hour to 0.001 to 1000 micrograms DDTC/ml. In contrast, in 7 human cell lines survival decreased steadily with increasing DDTC concentration (in the same dose range) without evidence of a biphasic pattern. These data might have implications for studies in which rodent cell lines are used to model the effects of dithiocarbamates in human tissues.
二乙基二硫代氨基甲酸盐(DDTC)和其他二硫代氨基甲酸盐目前作为传统化疗的潜在辅助药物而受到关注。对啮齿动物癌细胞系的体外研究一直表明,浓度为0.1 - 1.0微克/毫升的DDTC具有高度细胞毒性。然而,矛盾的是,浓度为10 - 100微克/毫升时毒性明显较小。在本研究中,当3种啮齿动物细胞系暴露于0.001至1000微克DDTC/毫升1小时时,再现了这种“双相”模式。相比之下,在7种人类细胞系中,随着DDTC浓度增加(在相同剂量范围内)存活率稳步下降,没有双相模式的证据。这些数据可能对使用啮齿动物细胞系模拟二硫代氨基甲酸盐在人体组织中的作用的研究有影响。