ANALYSIS OF THE OXIDATIVE CATABOLISM OF RETINOIC ACID IN RAT DUNNING R3327G PROSTATE TUMORS

We studied the enzymatic characteristics of the oxidative catabolism o f retinoic acid (RA) and its inhibition by liarozole-fumarate in homog enates of rat Dunning R3327G prostate tumors, Homogenates of rat liver were used as reference material. Both tumor and liver homogenates wer e able to catabolize retinoic acid. HPLC analysis revealed only very p olar metabolites in tumors, while in the liver both metabolites with i ntermediate polarity and more polar metabolites were found. Kinetic an alysis of retinoic acid catabolism showed a K-m of 1.7 +/- 0.7 mu M an d a V-max of 4.2 +/- 4.4 pmol polar RA metabolites/mg protein/hr for D unning G tumor homogenates. In liver homogenates a K-m value of 4.3 +/ - 0.5 mu M and a V-max value of 290 +/- 120 pmol polar RA metabolites/ mg protein/hr were obtained. Liarozole-fumarate inhibited retinoic aci d catabolism in Dunning tumors and liver with IC50 values of 0.26 +/- 0.16 mu M and 0.14 +/- 0.05, respectively. The results suggest that ra t Dunning R3327G tumors are able to metabolize retinoic acid in a mann er similar to that found in rat liver but with a lower metabolizing ca pacity. (C) 1996 Wiley-Liss, Inc.