MICROSOMAL ENZYMES AND THE TOXICITY OF THIONO-SULFUR COMPOUNDS

Abstract

This chapter provides an overview of microsomal enzymes. It discusses the toxicity of thiono–sulfur compounds. Thiono–sulfur containing compounds cause a number of toxic effects when administered to experimental animals and man. These effects include inhibition of thyroid hormone synthesis, induction of neoplasia, blood dyscrasias, liver necrosis, lung damage, teratogenesis, mutagenesis, inhibition of liver, lung, and brain cytochrome P-450 containing monooxygenases, and inhibition of copper containing enzymes. These toxic effects of thiono-sulfur containing compounds appear to be the result of their metabolism to reactive intermediates by the cytochrome P-450 containing monooxygenase enzyme systems. Covalent binding of atomic sulfur is responsible for the inhibition of monooxygenase activity and the loss of cytochrome P-450 seen on administration of thiono-sulfur compounds in vivo or incubation of cytochrome P-450 monooxygenase enzyme systems in vitro . Because of its extreme reactivity, the sulfur atom does not appear to bind to macromolecules other than cytochrome P-450. Therefore, the effects of these compounds are likely the result of the binding of the electrophilic S-oxides or S-dioxides to tissue macromolecules.