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MJ Pallardy, RV House and JH Dean
Department of Cellular and Molecular Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.
Previous studies in this laboratory have demonstrated that exposure of mice to the carcinogenic polycyclic aromatic hydrocarbon 7,12- dimethylbenz[a]anthracene results in suppression of both humoral and cell-mediated immunity. This suppression is unaccompanied by any significant alteration in splenic lymphocyte subpopulation composition, suggesting that the immune deficit was due to a modulation of lymphocyte function. Additional studies implicated the T helper lymphocyte as the probable target for 7,12-dimethylbenz[a]anthracene- induced immunosuppression, apparently through an inhibition of interleukin 2 production. The purpose of the present study was to examine the mechanism of 7,12-dimethylbenz[a]anthracene-induced T lymphocyte dysfunction at the molecular level and to determine the consequences of 7,12-dimethylbenz[a]anthracene exposure on the interleukin 2 pathway. In vitro exposure of Con A-activated splenocytes to 7,12-dimethylbenz[a]anthracene resulted in suppression of the mitogenic response, suppressed interleukin 2 production, and reduced the expression of the high affinity receptor for interleukin 2. In contrast, expression of the low affinity interleukin 2 receptor was not affected. In addition, interleukin 2-dependent lymphoblasts and long term cultured splenocytes exhibited a dose-dependent decrease in proliferation following in vitro exposure to 7,12- dimethylbenz[a]anthracene. These results suggest that 7,12- dimethylbenz[a]anthracene-induced immunosuppression may be mediated, at least in part, through the interleukin 2/interleukin 2 receptor pathway.
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