ABSTRACT. Pretreatment of primary cultures of rat hepatocytes with sodium diethyldithiocarbamate (DDTC) for 15 min prior to exposure to K 2 Cr 2 O 7 resulted in a marked decrease in dichromate-induced cytotoxicity, as evaluated by the leakage of lactate dehydrogenase, and in lipid peroxidation, as monitored by malondialdehyde formation. In addition, pretreatment with DDTC attenuated the suppression of the level of vitamin E attributed to K 2 Cr 2 O 7 . However, DDTC pretreatment had no effect on the cellular levels of glutathione or vitamin C or on the activity of the glutathione reductase, glutathione peroxidase, superoxide dismutase or alkaline phosphatase suppressed by dichromate. Under the same experimental conditions, cellular uptake or distribution of chromium was not affected by DDTC. These results indicate that the protective effect of DDTC on chromium (VI)-induced cytotoxicity as well as lipid peroxidation may be associated with the level of nonenzymatic antioxidants such as vitamin E. -KEY WORDS: chromium (VI), cytotoxicity, diethyldithiocarbamate, hepatocyte, lipid peroxidation.J. Vet. Med. Sci. 60(1): 71-76, 1998 associated in part with the production of active oxygen. Membrane-permeable metal-chelating agents such as deferoxamin (DFO) and o-phenanthroline (OP) have been reported to inhibit the DNA-strand breaks and cytotoxicity induced by hydrogen peroxide in cultured mammalian cells [8]. It is well known that these chelators form a complex with intracellular transition metals such as iron, preventing the occurrence of Fenton-type reaction of hydroxyl radical and protecting cells from the genetic and cytotoxic action of hydrogen peroxide [8]. With respect to chromium, recent studies showed that OP and DFO inhibited chromium (VI)-induced DNA breaks, cytotoxicity and lipid peroxidation in cultured cells [37,41] and that these chelators suppressed the formation of in vitro chromium (V) and chromium (V)-mediated hydroxyl radical [28,37].Diethyldithiocarbamate (DDTC) a metal chelator is used for the selective determination of chromium (VI) [30]. Furthermore, this chelator has also been shown to be an effecient inhibitor of Fe 2+ -and Cu 2+ -catalyzed hydroxyl radical formation, also protecting the cells from this toxic radical [46].In the present study, we using primary cultures of rat hepatocytes, to find examined whether DDTC has an effect on chromium (VI)-induced cytotoxicity and lipid Chromium (VI) compounds are potent toxic and carcinogenic metals [6]. With respect to their toxicity, hepatic and renal toxicities have been reported in workers and animals exposed to chromium (VI) [19]. Chromium (VI) compounds induced also DNA damage in vivo [5] and in cultured cells [36] as well as inhibition of the activity of such enzymes as glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) in mammalian cells [34].The biological effects of chromium (VI) are generally attributed to cellular uptake, since chromium (VI), in ...