Suppression of the in vitro immune response by 7,12-dimethylbenz[a]anthracene in mouse splenocytes co-cultured with rat hepatocytes.

7,12-Dimethylbenz[a]anthracene (DMBA) produced a dose-related suppression of in vitro polyclonal antibody response to lipopolysaccharide in mouse splenocytes co-cultured with rat hepatocytes. Addition of alpha-naphthoflavone (ANF), the cytochrome P-450 inhibitor, to the coculture reversed the DMBA-induced immunosuppression. The amount of [3H]DMBA bound to splenocyte DNA increased in a time-dependent manner up to 4 hr of co-culture and treatment of ANF reduced the binding. The addition of extracellular DNA to the co-culture prevented the suppression of the antibody response by DMBA. These results suggested that reactive metabolite(s) of DMBA were released from hepatocytes and that the suppression of the antibody response by DMBA is mediated via these reactive intermediate(s). DNA represents the primary macromolecular target for the reactive intermediate(s) of DMBA.