Direct suppression of in vitro antibody production by mouse spleen cells by the carcinogen benzo(a)pyrene but not by the noncarcinogenic congener benzo(e)pyrene.
The role of metabolic activation of benzo(a)pyrene B(a)P in mediating its suppression of humoral immune responsiveness of the female C57BL/6 X C3H F1 (hereafter called B6C3F1) mouse was addressed in these studies. The model was the in vitro antibody response by untreated splenic suspensions, to which was added directly either B(a)P or benzo(e)pyrene B(e)P. B(a)P suppressed the antibody response to DNP-Ficoll and sheep erythrocytes but not the polyclonal antibody response to LPS. This activity neither required nor was affected by addition of a metabolic activation system (i.e., S-9 crude liver homogenate from Aroclor-induced B6C3F1 mice) at 3 times the concentration (based on determination of protein content) which readily activated cyclophosphamide. Preliminary results with radiolabeled B(a)P verified that appreciable amounts of hydroxylated metabolites of B(a)P were obtained after only a 30-min preincubation. Therefore, production of the reactive metabolites of B(a)P which mediate its carcinogenicity are not essential for its immunosuppressive activity. The results, showing a parallel in the immunosuppressive profile of activity of B(a)P and the lack of immunosuppressive activity of B(e)P following in vivo and in vitro exposure, indicate that the in vitro antibody systems offer an ideal model system to characterize the PAHs.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism / Q000633:toxicity*; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D007165:Immunosuppression Therapy; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000378:metabolism
D001580:Benzopyrenes; D002273:Carcinogens; D001564:Benzo(a)pyrene; C026487:benzo(e)pyrene