Hepatocytes isolated from the adult male NMRI mouse or Wistar rat were incubated for 1 h with 0.5 mM 14C-benzene, the supernatant was separated from the cells, and analysed for benzene metabolites. Separately, formation of sulphate conjugates during benzene metabolism was studied in hepatocytes in the presence of 35S-sulphate. In addition sulphate conjugation of the benzene metabolites hydroquinone and 1,2,4-trihydroxybenzene was investigated in mouse liver cytosol supplemented with 3'-phosphoadenosine-5'-phospho-35S-sulphate. 2. Two novel metabolites, 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 35S-labelled conjugates could be demonstrated in incubations of mouse liver cytosol with hydroquinone or 1,2,4-trihydroxybenzene supplemented with 3'-phosphoadenosine-5'-phospho-35S-sulphate, and in mouse hepatocytes incubated with benzene and 35S-sulphate. 3. In comparison with hepatocytes from the Wistar rat, hepatocytes from the NMRI mouse were almost three times more effective in metabolizing benzene. The higher formation of hydroquinone, and the formation of trihydroxybenzene sulphate and hydroquinone sulphate, 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 towards the myelotoxic and leucaemogenic action of benzene.
摘要
从成年雄性NMRI小鼠或Wistar大鼠分离出的肝细胞与0.5 mM 14C-苯孵育1小时，将上清液与细胞分离，并分析苯代谢产物。另外，在35S-硫酸盐存在的情况下，研究了苯代谢过程中硫酸盐结合物的形成。此外，在补充了3'-磷酸腺苷-5'-磷酸-35S-硫酸盐的小鼠肝细胞溶胶中，研究了苯代谢产物对苯二酚和1,2,4-三羟基苯的硫酸盐结合作用。2. 在小鼠肝细胞中发现了两种在大鼠肝细胞孵育中未检测到的新代谢产物，它们被鉴定为1,2,4-三羟基苯硫酸盐和对苯二酚硫酸盐。在用对苯二酚或1,2,4-三羟基苯补充3'-磷酸腺苷-5'-磷酸-35S-硫酸盐的小鼠肝细胞溶胶孵育中，以及在用苯和35S-硫酸盐孵育的小鼠肝细胞中，均可证明35S标记结合物的形成。3. 与Wistar大鼠的肝细胞相比，NMRI小鼠的肝细胞代谢苯的效率几乎高三倍。对苯二酚的较高形成以及三羟基苯硫酸盐和对苯二酚硫酸盐的形成，主要导致了较高的苯代谢率。4. 总之，苯代谢的定性和定量差异可能导致小鼠对苯的骨髓毒性和致白血病作用的易感性更高。
