Abstract
1. We examined the effect of two chloro- s -triazines (atrazine and simazine) on hepatic microsomal cytochrome P450 enzymes in rat. Rats were treated intraperitoneally with atrazine or simazine daily for 3 days with 100, 200 and 400 mu mol kg. 2. Among the P450-dependent monooxygenase activities, testosterone 2 alpha -hydroxylase (T2AH) activity in rat, which is associated with CYP2C11, was significantly decreased at all doses of atrazine and simazine. The levels relative to control activities were 59-46 and 60-32% respectively. Similarly, oestradiol 2-hydroxylase (ED2H) activity was also significantly decreased by 28-51% by atrazine and simazine at all doses. However, no change in CYP2C11 protein level by either chloro- s -triazine was observed. K for T2AH m was significantly increased only by simazine (200 mu mol kg), whereas the V and Cl for max int T2AH were significantly decreased by atrazine and simazine at all doses. 3. 7-Ethoxyresorufin O -deethylase (EROD), 7-methoxyresorufin O -demethylase (MROD) and 7-pentoxyresorufin O -depentylase (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 400 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 showed that only simazine induces CYP1A2 and CYP4A1 2 protein expression. 4. Theactivities of 7-ethoxycoumarin O -deethylase (ECOD), bufuralol1-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 suggest that the pattern of changes in P450 isoforms by chloro- s triazinesdiffersbetweenatrazineandsimazine,thattheseherbicideschangetheconstitu and or male specific P450 isoform(s) in rat liver,and that these changes closely relate to the toxicity of chloro- s -triazines.
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