Maintenance of adult primate liver in organ culture: Potential use in toxicity testing

Adult Rhesus monkey liver slices were incubated using a dynamic organ culture method to determine hepatocyte viability, drug biotransformation potential and the in vitro response to the hepatotoxicant, allyl alcohol (AA). After 1, 2, 4, or 8 hr, slices were removed from culture and analyzed for incorporation of [3H]-leucine into acid-precipitable material, and medium alanine aminotransferase (ALT) activity was determined. Separate slices were taken for histological evaluation and for evaluation of microsomal 7-ethoxy-4-trifluoromethyl coumarin-O-deethylase (EFCOD) activity. Incorporation of [3H]-leucine into slices was linear over the period of incubation and was specifically inhibited by cycloheximide (10 uM) at all time points. In the absence of AA, enzyme leakage was minimal over 8 hr. Marked ALT leakage occurred with 1 mM AA. Control slices had an initial fall to 55% of in vivo EFCOD activity that stabilized at 40-50% control slices indicated that there was minimal cellular degeneration and that, in PAS-stained sections, glycogen accumulation occurred over the incubation period. This system allows for maintenance and viability of adult primate liver slices in culture for at least 8 hr and may be useful for in vitro toxicity and biotransformation studies