Sodium monochloroacetate causes cytotoxic effects, an increased lactate and pyruvate level and induces ultra structural and cytoskeletal alterations in cultured kidney and liver epithelial cells

1 Monochloroacetic acid (MCAA) and its sodium salt, sodium monochloroacetat e (SMCA) are widely used in chemical industries as intermediates in the syn thesis of carboxymethylcellulose, phenoxyacetic acid, thioglycolic acid, gl ycine, indigoid dyes and others. Moreover, MCAA has been found as a by-prod uct of the chlorination disinfection of drinking water and as an environmen tal contaminant of the atmosphere from the photodechlorination reactions of chlorinated hydrocarbons. Little is known about the mode of action of both compounds on the cellular level. From cases of accidental poisoning of man it is known that MCAA accumulates in liver and kidney, 2 In this study, the cytotoxicity of SMCA on cultured liver (Chang liver ce lls) and kidney epithelial cells of the proximal tubule (Opossum kidney cel ls) was investigated and its effect on metabolism, ultrastructure and organ ization of cytoskeleton was examined. 3 Independent from the growth state of the cells (proliferating or quiescen t), the results clearly show that SMCA causes a dose-dependent decrease in cell viability after an exposure period of 24 h. In all experiments, prolif erating cells were more sensitive than quiescent and confluent cells. Liver cells were less sensitive against SMCA treatment than kidney epithelial ce lls, In contrast to liver cells, kidney cells exhibited a dose-dependent de crease in cell volume, The decrease in cell viability was accompanied by an increase of lactate and pyruvate concentrations released into the culture medium. In the case of Opossum kidney cells, lactate and pyruvate levels in creased 5 - 6-fold, whereas in the case of Chang liver cells the increase w as approximately twofold. While the ultrastructure of liver cells remained unaltered after drug treatment, kidney cells exhibited cytoplasmic vacuoliz ation, membraneous disruption and especially mitochondrial alterations. In accordance with the changes in the ultrastructure of Opossum cells, was the reorganization of cytoskeletal elements with an increased stress fiber net work at the basolateral surface as web as a partial depolymerization of mic rotubules and vimentin filaments, A cytoskeletal reorganization was not obs erved for Chang liver cells after SMCA treatment. 4 The results demonstrate that SMCA causes a dose-dependent cytotoxicity wh ich is accompanied by metabolic, mitochondrial and cytoskeletal alterations in the cells.