EFFECTS OF TRIBUTYLTIN ON THE PHASE-I TESTOSTERONE-METABOLISM AND STEROID TITERS OF THE CLAM RUDITAPES DECUSSATA

The effects of tributyltin (TBT) on the cytochrome P450 monooxygenase system of the clam Ruditapes decussata have been evaluated. Digestive gland microsomes were observed to catalyze the oxidative metabolism of testosterone. The metabolites detected were androstenedione, dihydrot estosterone, dihydroandrostenedione, 6 beta-, 6 alpha-, 2 alpha- and 2 beta-hydroxytestosterone, estrone and 17 beta-estradiol. The effect o f 0.1 and 1.0 mM TBT in the incubation mixture lead to a significant r eduction in the total metabolism rate (28-39%) and changes in the meta bolite profile, viz. a significant decrease in the formation of andros tenedione (51-54%) and a stimulation in the formation of hydroxylated metabolites. To fully understand and validate the in vitro data, clams were exposed to different concentrations of TBT in water (0.1, 0.45 a nd 2.27 mu g l(-1) of TBT as Sn) for 7 days. When digestive gland micr osomes of control and exposed organisms were assayed for their ability to metabolize testosterone, important changes were observed in the pa ttern of the metabolites formed. There was a significant increase in t he formation of 6 alpha-hydroxytestosterone and a dose-dependent decre ase in the aromatization of testosterone to estrone and estradiol. Mor eover, investigation of steroid concentrations by radioimmunoassay rev ealed an increase in testosterone in the tissue of TBT-exposed clams. These observations indicate a significant interaction of TBT with andr ogen metabolism in the clam Ruditapes decussata which may contribute t o the masculinization of clam physiology. (C) 1998 Elsevier Science B. V. All rights reserved.