Effect of 3-Amino-1,2,4-Triazole Pretreatment on N - and Ring-Hydroxylation of 2-Acetylaminofluorene by the Rat 1

Summary

(1) Pretreatment of adult male rats with aminotriazole (1 g/kg body wt./day) for 9 days produced severalfold increase compared to control group in the urinary excretion of N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF) after ip administration of a test dose of AAF. Such a treatment also increased appreciably the urinary excretion of ring-hydroxy metabolites of AAF. (2) Effects of bile-duct ligation of adult male rats on the urinary excretion of hydroxy metabolites of AAF were similar to the effects of aminotriazole pretreatment. The urinary excretion pattern of these metabolites was about the same in both bile-duct ligated groups with or without aminotriazole treatment. (3) Ring-hydroxylation of AAF by liver microsomes was inhibited by 25% in aminotriazole treated group compared to the controls. (4) Aminotriazole (1 g/kg body wt./day) treatment of rats for 3 days inhibited enzymatic esterification of N-hydroxy-AAF by liver cytosol preparations by about 25%.