Effect of methylcholanthrene on human natural killer cell cytotoxicity and lymphokine production in vitro

We have developed a simple culture assay system for measuring the in vitro effects of a chemical carcinogen, 3-methylcholanthrene (MCA), on certain activities of human peripheral blood lymphocytes: blastogenesis, cell-mediated cytotoxicity by natural killer cells, interleukin-2 production, lymphotoxin release and percent T-cell subpopulations. After 72 h of treatment with different doses of MCA, blastogenesis was suppressed 23-87% and cell-mediated cytotoxicity was inhibited 45-90%. Interleukin-2 and lymphotoxin production were decreased by 64% and 38%, respectively. On the other hand, MCA treatment at the same doses caused no significant change in the percent of T-cell subsets. We conclude that MCA exerts an inhibitory effect on T-cell functional activity such as interleukin-2 and lymphotoxin production which correlate with a suppression of blastogenesis and natural killer cell activity. This in vitro assay system could be important for future studies in explaining specific inhibitory effects of chemical carcinogens on lymphoid cell function relative to tumorigenesis.