EFFECTS OF TRIBUTYLTIN CHLORIDE INVITRO ON THE HEPATIC-MICROSOMAL MONOOXYGENASE SYSTEM IN THE FISH STENOTOMUS-CHRYSOPS

Tributyltin (TBT) has been shown to be highly toxic to a number of aquatic species, but the mode(s) of action on a biochemical level remain(s) to be elucidated. Here we investigate the interaction in vitro of TBT with hepatic microsomal cytochrome P-450 and associated enzyme activity in scup (Stenotomus chrysops). Hepatic microsomes from beta-naphthoflavone (beta-NF) induced scup were incubated in vitro with TBT and various components analyzed. TBT led to a time- and concentration-dependent decrease in total microsomal P-450 content. This decrease was accompanied by the formation of cytochrome P-420. A complete loss of P-450 occurred with 1 mM TBT after 30 min incubation. Ethoxyresorufin-O-deethylase (EROD) activity was strongly inhibited by TBT in a concentration-dependent manner, with a complete inhibition at 0.3 mM TBT after 15 min incubation. Other components of the microsomal electron transport system were also investigated. Neither cytochrome b5 content, nor NADPH-cytochrome c reductase activity were affected by TBT at concentrations up to 0.5 mM TBT. NADH-cytochrome c reductase activity, however, showed a concentration-dependent increase, with more than a doubling of activity at 0.5 mM TBT. This indicates that TBT has different effects on these reductases. In conclusion, TBT can strongly interact with hepatic microsomal P-450 in fish leading to destruction of native enzyme and inhibition of enzyme activity.