Effects of aspirin on the in vitro and in vivo acetylation of 2-aminofluorene in Sprague-Dawley rats.

The present study was undertaken to determine the effect of acetylsalicylic acid acid on the in vitro N-acetyltransferase (NAT) enzyme activity and in vivo acetylation of 2-aminofluorene in laboratory rats. In the in vitro experiments, cytosols of blood, bladder, colon and liver cells, with or without acetylsalicylic acid co-treatment, showed different percentages of 2-aminofluorene acetylation. The data indicated that there was decreased NAT activity associated with increased acetylsalicylic acid in the cytosol reaction. In the in vitro experiments, values of apparent Km and Vmax decreased by 4% and 21%, respectively, for acetylation of AF in blood NAT, 28% and 31% for acetylation of AF in bladder NAT, 12% and 25% for acetylation of AF in colon NAT, and 50% and 35% for acetylation of AF in liver NAT. In the in vivo experiments, pretreatment with acetylsalicylic acid (50 mg/kg) 48 h prior to the administration of 2-aminofluorene (50 mg/kg) resulted in 24% and 28% decreases in the fecal and urinary recovery of N-acetyl-2-aminofluorene and a 26% decrease in the metabolic clearance of 2-aminofluorene to N-acetyl-2-aminofluorene. This is the first demonstration of acetylsalicylic acid (Aspirin) inhibition of arylamine N-acetyltransferase activity showing decreases in the N-acetylation of carcinogens in vivo.