In vitro comparative toxicity of selected drugs and chemicals in HeLa cells, Chang liver cells, and rat hepatocytes.

The cytotoxicity of 16 agents was compared in four different in vitro cellular systems: HeLa cells, Chang liver cells, freshly isolated rat hepatocytes in suspension, and primary monolayer cultures of postnatal rat hepatocytes. The compared cytotoxicity values had been obtained by different techniques: inhibition of spreading of HeLa cells by 50% after 24 hr 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 hr incubation with the chemicals. Carbon tetrachloride, halothane, acetaminophen, and tetracycline were more toxic to the hepatocytes compared with the two cell lines. Alcohol, sodium salicylate, caffeine, papaverine, nitrofurantoin, and five tricyclic antidepressants 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.