In vitro Comparative Toxicity of Selected Drugs and Chemicals in HeLa Cells, Chang Liver Cells, and Rat Hepatocytes

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Abstract
The cytotoxicity of 16 agents was compared in 4 different in vitro cellular systems: HeLa [human cervical carcinoma] cells, Chang [human] liver cells, freshly isolated rat hepatocytes in suspension and primary monolayer cultures of postnatal rat hepatocytes. The compared cytotoxicity values were obtained by different techniques: inhibition of spreading of HeLa cells by 50% after 24 h incubation and leakage of lactate dehydrogenase (LDH) by 50% in Chang liver cells, isolated rat hepatocytes in suspension, and primary cultures of rat hepatocytes after 4, 1 and 3 or 24 h incubation with the chemicals. CCl4, halothane, acetaminophen and tetracycline were more toxic to the hepatocytes compared with the 2 cell lines. Alcohol, sodium salicylate, caffeine, papaverine, nitrofurantoin and 5 tricyclic antidepressants [chlorimipramine, desipramine, nortriptyline, imipramine and amitriptyline] showed similar toxicity in all compared cellular systems. Thus, the agents with a known or suspected metabolism-mediated liver toxicity indeed had a high differential hepatotoxicity in vitro.