CHARACTERIZATION OF THE CYP ISOZYME PROFILE INDUCED BY CYCLOHEXANOL

In a previous report we described the ability of cyclohexanol to induc e CYP activity. In order to characterize this induction we tested the capacity of liver S9 from rats orally treated with cyclohexanol for 5 days, to activate several carcinogenic nitrosamines into mutagens in t he Salmonella typhimurium TA100 test system, Additionally, Western blo t analysis of hepatic microsomes from the same treated animals were an alysed with specific antibodies against P450 protein families 1A1/A2, 2B1/B2 and 2E1, Cyclohexanol-S9 mixture was more efficient in activati ng the following nitrosamines: N-nitrosodimethylamine (NDMA), N-nitros odipropylamine (NDPA), N-nitrosomethylpropylamine (NMPA), N-nitrosodib utylamine (NDBA), and N-nitrosopyrrolidine (NPYR) into bacterial mutag ens than S9 from non-treated animals, The mutagenicity of N-nitrosodie thylamine (NDEA) was not modified in the presence of S9 from cyclohexa nol-treated animals, Since the main metabolic pathway leading to the p roduction of mutagenic intermediates of NDMA and NPYR is catalysed by isozyme CYP2E1 and that of NDPA, NMPA and NDBA by CYP2B1/B2, mutagenic ity experiments predicted that cyclohexanol induces these two P450 iso zyme families, Western blot analysis confirmed the results of the muta genicity assay, showing an increase in the intensity of CYP2E1 and CYP 2B1/B2 protein bands in hepatic microsomes from cyclohexanol treated r ats in comparison with non-treated controls, Bacterial mutagenicity te sts with specific pro-mutagens were good predictors of the P450 induct ion properties of cyclohexanol.