Evaluation of hepatocytes isolated by a nonperfusion technique in a prescreen for cytotoxicity.

Abstract

Twenty-three chemicals, differing widely in cytotoxic (hepatotoxic) potency in vivo, were examined to determine their ability to release glutamic-oxaloacetic transaminase (GOT) from hepatocytes isolated by a nonperfusion method from rat liver. The test chemicals were carbon tetrachloride, chloroform, 1,1,2- and 1,1,1-trichloroethane, six bromobenzene analogs, tri-n-butyl tin, chlorpromazine, tetracycline, halothane, phenobarbital, L-ethionine, acetaminophen, thioacetamide, allyl alcohol, ethanol, ascorbic acid, dimethyl sulfoxide, and acetone. In all but two cases--thioacetamide and allyl alcohol--there was a good correspondence between chemicals active in the assay as now performed and those that elevate serum transaminase and cause liver injury on short-term exposure in vivo. These results indicate that with further effort it may be possible to develop an effective, inexpensive, and rapid prescreen to identify drugs and environmental chemicals that are potentially cytotoxic to animals and humans.