CHANGES IN RAT-LIVER CYTOCHROME-P450 ENZYMES BY ATRAZINE AND SIMAZINETREATMENT

1. We examined the effect of two chloro-s-triazines (atrazine and sima zine) on hepatic microsomal cytochrome P450 enzymes in rat. Rats were treated intraperitoneally with atrazine or simazine daily for 3 days w ith 100, 200 and 400 mu mol/kg. 2. Among the P450-dependent monooxygen ase activities, testosterone 2 alpha-hydroxylase (T2AH) activity in ra t, which is associated with CYP2C11, was significantly decreased at al l doses of atrazine and simazine. The levels relative to control activ ities were 59-46 and 60-32% respectively. Similarly, oestradiol 2-hydr oxylase (ED2H) activity was also significantly decreased by 28-51% by atrazine and simazine at all doses. However, no change in CYP2C11 prot ein level by either chloro-s-triazine was observed. K-m for T2AH was s ignificantly increased only by simazine (200 mu mol/kg), whereas the V -max and Cl-int for T2AH were significantly decreased by atrazine and simazine at all doses. 3. 7-Ethoxyresorufin O-deethylase (EROD), 7-met hoxyresorufin O-demethylase (MROD) and 7-pentoxyresorufin O-depentylas e (PROD) activities were significantly increased by 1.4-1.6-, 1.7-3.2- and 1.5-2.2-fold respectively, by both chloro-s-triazines at 200 or 4 00 mu mol/kg. Lauric acid omega-hydroxylase (LAOH) was also increased by 1.4-fold by simazine at 200 and 400 mu mol/kg. Immunoblotting showe d that only simazine induces CYP1A2 and CYP4A1/2 protein expression. 4 . The activities of 7-ethoxycoumarin O-deethylase (ECOD), bufuralol 1' -hydroxylase (BF1'H), chlorzoxazone 6-hydroxylase (CZ6H), testosterone 6 beta-hydroxylase (T6BH) and testosterone 7 alpha-hydroxylase (T7AH) were not affected by either chloro-s-triazine, 5. These results sugge st that the pattern of changes in P450 isoforms by chloro-s-triazines differs between atrazine and simazine, that these herbicides change th e constitutive and/or male specific P450 isoform(s) in rat liver, and that these changes closely relate to the toxicity of chloro-s-triazine s.