Bg. Lake et al., EFFECT OF PEROXISOME PROLIFERATORS AND INDUCERS OF XENOBIOTIC METABOLISM ON MARKER ENZYME-ACTIVITIES IN CULTURED RAT-LIVER SLICES, Toxicology in vitro, 8(4), 1994, pp. 521-523
Previous work has demonstrated that precision-cut liver slices represe
nt a valuable in vitro system for studying the metabolism and toxicity
of xenobiotics. We have investigated their use for enzyme induction s
tudies. Liver slices were prepared from male Sprague-Dawley rats and b
y using a dynamic culture system could be maintained in RPMI 1640 medi
um for up to 72 hr. The addition of 0.02-0.5 mM concentrations of cipr
ofibrate, nafenopin and Wy-14,643 for 48 and 72 hr produced a concentr
ation and time dependent induction of palmitoyl-CoA oxidation and carn
itine acetyltransferase activities. Ultrastructural examination of liv
er slices revealed an increase in the number of peroxisomes. Liver sli
ces were also cultured with 0.2-5 mM phenobarbitone, 5-50 mu M beta-na
phthoflavone and 0.5-20 mu g Aroclor 1254/ml and effects on the metabo
lism of 7-ethoxycoumarin, 7-benzoxyresorufin and 7-ethoxyresorufin det
ermined. All three compounds produced a concentration and time depende
nt induction of mixed-function oxidase enzyme activities. The results
of this study demonstrate that rat liver slices can be cultured for up
to 72 hr and appear to retain functional viability in that they respo
nd to some known peroxisome proliferators and inducers of xenobiotic m
etabolism. Cultured liver slices may thus be a useful alternative in v
itro system to hepatocytes for screening compounds for effects on vari
ous enzyme activities.