A biochemical study of the toxicity of S-dichlorovinyl- l-cysteine

Abstract

A study has been made of the biochemical effects of S-dichlorovinyl- l-cysteine (DCVC) and the corresponding mercaptopropionic acid (DCVMP) and cysteamine (DCVCA) derivatives in the rat and guinea-pig. In rat-kidney slice experiments using glucose as substrate DCVC and DCVMP inhibited respiratory activity at a concentration of the order of 10 −3M. DCVCA was without effect. The inhibitory action of DCVC was also demonstrated on guinea-pig kidney slices. Loss of respiratory activity was accompanied by increased levels of pyruvic and lactic acids in the incubation medium. With liver and kidney mitochondria from both species moderate or substantial inhibition of both unstimulated and dinitrophenol (DNP)-stimulated respiration occurred appropriate to the concentration of DCVC in the medium. Similar results were obtained with DCVMP in both types of rat mitochondria but DCVCA, however, exercised no effect on rat-kidney mitochondrial respiration. Intraperitoneal doses of 50 mg DCVC/kg impaired DNP-stimulated respiration of rat-kidney mitochondria which persisted for over 48 hr and could not be reversed by simple washing techniques. With 15 mg DCVMP/kg administered intraperitoneally the effect on DNP-stimulated respiration was both less marked and less persistent. There was no evidence to suggest that DCVC or DCVMP acts as an alkylating agent. The incorporation of 14C-labelled amino acids into protein of the pancreas, but not of the liver or kidney, was inhibited by intraperitoneal administration of DCVC. DCVMP also inhibited amino acid uptake into pancreatic and in addition kidney protein. These and other observations seem to indicate that the amino acid character of DCVC is not important with regard to its toxicity which is possibly mediated at the mitochondrial level.