© 1983 Oxford University Press
research-article |
Potentiation of Chlorinated Hydrocarbon Toxicity by 2,5-Hexanedione in Primary Cultures of Adult Rat Hepatocytes
ADepartment of Pharmacology, Venderbilt University Nashville, Tennessee BFood and Drug Administration, National Center for Toxicological Research Jefferson, Arkansas 72079 CDivision of Interdisciplinary Toxicology, University of Arkansas for Medical Sciences Little Rock, Arkansas 72205
Potentiation of Chlorinated Hydrocarbon Toxicity by 2,5-Hexanedione in Primary Cultures of Adult Rat Hepatocytes. Jernigan, James D., Pounds, Joel G. and Harbison, Raymond D. (1983). Fundam. Appl. Toxicol. 3:22-26. Primary cultures of adult rat hepatocytes were used to investigate potentiation of halocarbon-induced hepatotoxicity by aliphatic ketones. Male Sprague-Dawley rats were pre-treated with corn oil or 2,5-hexanedione (HD; 15 mmol/kg, po) in corn oil. Eighteen hours later the hepatocytes were isolated and cultured in Williams' Medium E and exposed to several concentrations of the hepatotoxicants carbon tetra-chloride, chloroform, deutero-chloroforra, or 1,1,2-trichloroethane. The cytotoxicity of these halocarbons as measured by release of the cytosolic enzyme lactate dehydrogenase into the culture medium was both time- and concentration dependent. Halocarbon-induced cytotoxicity was exacerbated in cells isolated from HD-pretreated rats with significant increases in LDH release over cells isolated from corn oll-pretreated rats. In addition, chloroform was significantly more toxic than deutero-chloroform in hepatocytes from either corn oil- or HD-pretreated rats. Primary monolayer cultures were useful for studying ketone-induced potentiation, halocarbon-induced hepatocellular toxicity, and the mechanisms by which these effects occur.