Effects of chlorinated solvents on the natural lymphocytotoxic activities of human liver immune cells.

Inhibition of the natural immune system may be involved in the liver cancer caused by some non-genotoxic chemicals when they are administered at high doses to certain strains of animals. Previous studies have shown that some chlorinated solvents inhibit liver natural immune function in rodents. In this preliminary study, the effects of in vitro exposure to three commonly used chlorinated solvents were determined on three tumoricidal activities expressed by isolated human liver immune cells-natural killer (NK), natural cytotoxic (NC) and natural P815 killer (NPK) (Wright and Stacey, 1991) cell activities. The NK, NC and NPK cell activities of immune cells isolated from three human livers were 115, 45 and 53 lytic units (LU(20%)/10(6) effector cells), respectively. In vitro exposure to trichloroethylene (TRI) inhibited all three natural immune activities, and the ranking of sensitivity was NPK NC NK. Tetrachloroethylene (TET) inhibited NC and NPK cell activities, but had little effect on NK cell activity. 1,1,1-Trichloroethane (TCE) had little or no effect on the three tumoricidal activities examined. Overall, these data show clear similarities to the results obtained in vitro using cells from experimental animals.

Effects of tetrachloroethylene on hepatic and splenic lymphocytotoxic activities in rodents.

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.