Irreversible inhibition of the cytosolic metabolism of N-hydroxy-2-acetylaminofluorene by its glycolyl analog.
Lim-LO; Corbett-BR; Corbett-MD
Cancer Lett 1987 Oct; 37(2):205-211
The cytosolic metabolism of 2-aminofluorene (153786) (AF) derivatives was studied in liver microsomal fractions obtained from Sprague-Dawley-rats. Microsomal fractions were incubated with either ethanol (2.5 to 10 microliters) as control, or 10 millimolar (mM) N- hydroxy-2-acetylaminofluorene (53952) (NOHAAF) or N-hydroxy-2- glycolylaminofluorene (NOHGAF) in ethanol. The supernatant was analyzed to determine substrate disappearance and 2- acetylaminofluorene (53963) (AAF) formation by high pressure liquid chromatography. NOHAAF was rapidly metabolized by cytosolic enzymes. AAF appeared concomitantly with the disappearance of NOHAAF. At 2 hours, the amount of AAF was 45 percent of the original amount of NOHAAF. Only 25 percent of the initially added NOHGAF was consumed within 1 hour. No further decrease in NOHGAF was observed in up to 2 hours of incubation. The results indicated that NOHGAF inhibited its own metabolism. The liver cytosolic fraction was preincubated with NOHGAF (0 to 20 micromolar) for up to 60 minutes and after addition of NOHAAF, the rate of NOHAAF metabolism was determined. Results showed that NOHGAF inhibited both disappearance of NOHAAF and formation of AAF. NOHGAF inactivation of the cytosolic enzymes was irreversible. Microsomal enzymes metabolized NOHAAF and NOHGAF to a similar extent with no obvious inactivation of the enzymes. The results indicated a suicide inhibition type of metabolism for NOHGAF in rat liver cytosol. No such effect was observed in the microsomal fraction.
NIOSH-Publication; NIOSH-Grant; Cancer; In-vitro-studies; Laboratory-animals; Cell-metabolism; Fluorenes; Liver-cells; Microsomal-enzymes; Oxidative-enzymes; Liver-microsomal-metabolism
Food Science & Human Nutrition Univeristy of Florida Gainesvile, FL 32611 Gainesville, Florida 32611
153-78-6; 53-95-2; 53-96-3
University of Florida, Gainesville, Florida