ROLE OF METABOLISM IN ETHYL CARBAMATE-INDUCED SUPPRESSION OF ANTIBODY-RESPONSE TO SHEEP ERYTHROCYTES IN FEMALE BALB C MICE/

A possible role of metabolism by cytochrome P450 (P450) in ethyl carba mate-induced suppression of the antibody response to a T-cell-dependen t antigen, sheep erythrocytes (SRBCs), was investigated in female Balb /C mice. When mice were treated with ethyl carbamate intraperitoneally for 14 consecutive days at 25, 50, 100, 200 and 400 mg/kg, the antibo dy response was significantly suppressed from 200 mg/kg. These doses a lso caused a decrease in thymus weight. An acute dosing of ethyl carba mate at 1 g/kg also caused not only a significant suppression of the a ntibody response, but also a decrease in thymus weight. The antibody r esponse was most likely to be the IgM antibody response, which was dem onstrated in a haemagglutination study. When mice were pretreated with phenobarbital (80 mg/kg) for 3 days to induce P450 enzymes, followed by administration of ethyl carbamate intraperitoneally for 7 consecuti ve days, the antibody response was more suppressed than in saline-pret reated controls. Moreover, a study using aminoacetonitrile, a P450 inh ibitor, showed that the antibody response suppressed by ethyl carbamat e was completely recovered by the inhibitor. The present results sugge st that metabolism of ethyl carbamate by P450 may be the critical path way to produce metabolites capable of suppressing the antibody respons e.