Rj. Price et al., COMPARISON OF THE TOXICITY OF ALLYL ALCOHOL, COUMARIN AND MENADIONE IN PRECISION CUT RAT, GUINEA-PIG, CYNOMOLGUS MONKEY AND HUMAN LIVER SLICES, Archives of toxicology, 71(1-2), 1996, pp. 107-111
The toxicity of allyl alcohol, coumarin and menadione has been studied
in precision-cut liver slice cultures. Liver slices were prepared fro
m male Sprague-Dawley rats, male Dunkin-Hartley guinea-pigs and from s
amples of Cynomolgus monkey and human liver using a Krumdieck tissue s
licer. The liver slices were cultured with the test compounds for 24 h
in a dynamic organ culture system. Toxicity was assessed by measureme
nt of protein synthesis, potassium content and the MTT assay. At the c
oncentrations examined, menadione produced marked toxicity in liver sl
ices from all four species, whereas rat liver slices were less suscept
ible to allyl alcohol toxicity. Coumarin produced concentration-depend
ent toxic effects in rat and guinea-pig liver slices, whereas Cynomolg
us monkey and human liver slices were relatively resistant, especially
at low coumarin concentrations. At some concentrations of the test co
mpounds examined, the MTT assay appeared to be a less sensitive indica
tor of toxicity than either protein synthesis or potassium content. Th
ese results demonstrate the usefulness of precision-cut liver slices f
or assessing species differences in xenobiotic-induced toxicity.