Effects of tributyltin on the Phase I testosterone metabolism and steroid titres of the clam Ruditapes decussata

Abstract

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, dihydrotestosterone, dihydroandrostenedione, 6 β-, 6 α-, 2 α- and 2 β-hydroxytestosterone, estrone and 17 β-estradiol. The effect of 0.1 and 1.0 mM TBT in the incubation mixture lead to a significant reduction in the total metabolism rate (28–39%) and changes in the metabolite profile, viz. a significant decrease in the formation of androstenedione (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 and 2.27 μg l −1 of TBT as Sn) for 7 days. When digestive gland microsomes of control and exposed organisms were assayed for their ability to metabolize testosterone, important changes were observed in the pattern of the metabolites formed. There was a significant increase in the formation of 6 α-hydroxytestosterone and a dose-dependent decrease in the aromatization of testosterone to estrone and estradiol. Moreover, investigation of steroid concentrations by radioimmunoassay revealed an increase in testosterone in the tissue of TBT-exposed clams. These observations indicate a significant interaction of TBT with androgen metabolism in the clam Ruditapes decussata which may contribute to the masculinization of clam physiology.