Induction of immunotoxicity by polycyclic hydrocarbons: role of the Ah locus.

Abstract

We have employed the plaque forming cell (PFC) response to sheep erythrocytes as well as lymphocyte proliferation to study the induction of immunotoxicity in AHH-inducible (Ah Locus positive, C57BL/6N; B6C3F1) and AHH non-inducible (Ah Locus negative, DBA2/N) mice following administration of polycyclic aromatic hydrocarbons. When two potent carcinogenic polycyclic hydrocarbons which induce AHH activity, 3-methylcholanthrene (MCA) or 1,2,5,6-dibenzanthracene [DB(a,h)A] were administered IP, immunotoxicity was observed in both AHH-inducible and AHH non-inducible animals. However, the AHH-inducible animals appeared to be more sensitive, and substantial suppression of a PFC response toxicity could be induced with doses as low as 14 mg/kg methylcholanthrene. While suppression of a mitogen response required a dose of 43-125 mg/kg. Administration of the weak carcinogen 1,2,3,4-dibenzanthracene [DB(a,c)A], IP, which similarly induces AHH activity in inducible animals, failed to induce immunotoxicity in either C57B1/6N or DBA/2N mice. In contrast to the results obtained following IP administration, when MCA was administered repeatedly (4X) via an intragastric (IG) route we observed striking immunosuppression of a PFC response in Ah locus negative (DBA/2) animals but minimal effects in Ah locus positive animals (C57B1/6). We finally observed that a single IP dose of MCA (125 mg/kg) to Ah locus positive animals substantially inhibited Natural Killer Cell activity but had more limited effects on the ability of an animal to reject a challenge by an immunogenic syngeneic fibrosarcoma.