BENZENE METABOLISM IN RODENT HEPATOCYTES - ROLE OF SULFATE CONJUGATION

1. Hepatocytes isolated from the adult male NMRI mouse or Wistar rat w ere incubated for 1 h with 0.5 mM C-14-benzene, the supernatant was se parated from the cells, and analysed for benzene metabolites. Separate ly, formation of sulphate conjugates during benzene metabolism was stu died in hepatocytes in the presence of S-35-sulphate. In addition sulp hate conjugation of the benzene metabolites hydroquinone and 1,2,4-tri hydroxybenzene was investigated in mouse liver cytosol supplemented wi th 3'-phosphoadenosine-5'-phospho-(35)-sulphate. 2. Two novel metaboli tes, not detectable in rat hepatocyte incubations, were found in mouse hepatocytes, and were identified as 1,2,4-trihydroxybenzene sulphate and hydroquinone sulphate. Formation of the S-35-labelled conjugates c ould be demonstrated in incubations of mouse liver cytosol with hydroq uinone or 1,2,4-trihydroxybenzene supplemented with 3'-phosphoadenosin e-5'-phospho-S-35-sulphate, and in mouse hepatocytes incubated with be nzene and S-35-sulphate. 3. In comparison with hepatocytes from the Wi star rat, hepatocytes from the NMRI mouse were almost three times more effective in metabolizing benzene. The higher formation of hydroquino ne, and the formation of trihydroxybenzene sulphate and hydroquinone s ulphate, mainly contributed to the higher rate of benzene metabolism. 4. In conclusion, qualitative and quantitative differences in benzene metabolism may contribute to the higher susceptibility of mouse toward s the myelotoxic and leucaemogenic action of benzene.