Schlichting L M, Wright P F, Stacey N H
Toxicology Unit, National Institute of Occupational Health and Safety Worksafe Australia, University of Sydney, NSW.
Toxicol Ind Health. 1992 Sep-Oct;8(5):255-66.
The industrial solvent tetrachloroethylene (TCE) is a liver carcinogen in experimental animals but is without significant genotoxicity. Presumably some nongenotoxic mechanism accounts for its cancer-causing effects. We have therefore investigated the effects of TCE on splenic and hepatic lymphocytotoxic activities in Sprague-Dawley rats and B6C3F1 mice, following in vivo and in vitro exposure to TCE. Natural killer (NK), natural cytotoxic, and "natural P815 killer" activities were measured in liver- and spleen-derived immune cells. Humoral and T-cell mitogenesis were assayed in lipopolysaccharide and Con-A-stimulated splenic cells, respectively. TCE administration in vivo did not significantly alter the various immunological parameters assessed, while in vitro exposure to TCE inhibited natural cytotoxic activity from liver and spleen in mice and rats. NK and "natural P815 killer" activity in rat cells exposed in vitro to TCE were also inhibited. Thus, TCE is capable of directly inhibiting natural lymphocytotoxic activity, which is indicated by these in vitro effects. While an inhibitory effect was not observed when immune cells were isolated from in vivo treated animals, the in vitro data do support the possibility that a direct inhibition of natural immune function may play some role in the carcinogenic effects of TCE in experimental mice.
工业溶剂四氯乙烯（TCE）在实验动物中是一种肝脏致癌物，但没有明显的基因毒性。据推测，其致癌作用是由一些非基因毒性机制引起的。因此，我们研究了TCE在体内和体外暴露于TCE后对Sprague-Dawley大鼠和B6C3F1小鼠脾脏和肝脏淋巴细胞毒性活性的影响。在源自肝脏和脾脏的免疫细胞中测量自然杀伤（NK）、自然细胞毒性和“自然P815杀伤”活性。分别在脂多糖和Con-A刺激的脾细胞中检测体液和T细胞有丝分裂原。体内给予TCE并没有显著改变所评估的各种免疫参数，而体外暴露于TCE会抑制小鼠和大鼠肝脏和脾脏的自然细胞毒性活性。体外暴露于TCE的大鼠细胞中的NK和“自然P815杀伤”活性也受到抑制。因此，TCE能够直接抑制自然淋巴细胞毒性活性，这些体外效应表明了这一点。虽然从体内处理的动物中分离免疫细胞时未观察到抑制作用，但体外数据确实支持直接抑制自然免疫功能可能在TCE对实验小鼠的致癌作用中发挥一定作用的可能性。
