ABSTRACT.Effects organic mercurials (PCMBS, PCMB, mersalyl) an alkylating reagent (NEM), disulphide reagents (DTP, CPDS) and the dithiocarbamate agent DSF (disulfiram) were studied in hepatocyte culture. Cytotoxicity, was on a high level (organic mercurials), moderate (NEM, DTP), or none (DSF, CPDS). The organic mercurials and NEMinduced glutathione depletion. Disulphide compounds were detoxified by metalJothionein binding. Organic mercurials inhibited the cellular glucose uptake. The most prominent effect of NEM, DTPand DSFwas an inhibition of the TCA-cycle. The hepatocellular BSP metabolism was delayed by all tested compounds. Albumin synthesis was stimulated by pyruvate and blocked by PCMBand PCMBS,by inhibiting the hepatocellular amino acid uptake. Phase I and II biotransformation reactions were inhibited by PCMBS and PCMBby direct binding to Cyt. P450 cysteinyl-residues and active sites of UDP-glucuronyltransferases. DSF probably reacts by diminishing the availability of the co factor NADPH. Isolated ALDH(EC 1.2.1.3) was inhibited by all studied compounds. In cellular systems, DSF and the organomercurials inhibited ALDH,thereby reducing the cell's capacity of ethanol catabolism. All tested compounds showed, in low doses, the anabolic ability of insulin mimicking, as demonstrated in a balanced endocrine in vitro testsystem. Morphology. Exposure to NEM,DTP, CPDS, DSF did not result in any morphological alterations in the cell cultures. However, an exposure to PCMBSand PCMB, resulted in extensive bleb-formation, as a result of SHgroup blocking at the cell's outer membrane. It can be concluded, that cultured hepatocytes from human or rat origin, resist an exposure to alkylating and disulphide SH-reagents up to relatively high dose (1.0 mM). However, organic mercury compoundstriggered an extensive bleb formation, as a result of SH-blocking, thereby disturbing the osmotic balance by blocking Na+/K+carriers. Of all tested reagents, organic mercury compounds arose as the most toxic reagents.Hepatocytes in short-term and primary cultures are now being widely used in toxicological studies and offer many advantages, in studying the hepatic metabolism of endogeneous substances and xenobiotics (3-12, 14-17, 29, 33, 35). Cell membranes are intact, a relatively pure cell population can be isolated and the culture medium is in direct contact with the cells and replicate experiments can be performed, using genetically identical material. In addition to biochemical analysis, phasecontrast microcopy and electron-microscopical analysis, are interesting additional techniques. The purpose of the present study, is to describe toxicological data of SH-reagents. Effects of organic mercurials (PCMBS, PCMB, mersalyl) an alkylating reagent (NEM), disulphide reagents (DTP, CPDS) and the dithiocarbamate reagent DSF (disulfiram), were studied in vitro. Effects were compared with standard inhibitors of the physiological parameters studied. As a biological system, rat hepatocyte short term and primary cultures were used as well as humanh...