Comparison of xenobiotic-mediated cytotoxicity in rat cultured hepatocytes and V79 Chinese hamster lung fibroblast cell line: can metabolically-activated hepatotoxins be identified by selective cytotoxicity to hepatocytes?

By Fry, J.R. - Hammond, A.H. - Garle, M.J. - Lal, K.

The effects of 17 xenobiotics on rat hepatocytes and V79 cells were evaluated under identical exposure conditions (confluent monolayer for 24 hours) and endpoint measurement (MTT reduction). The data indicated that the majority of metabolically-activated rat hepatotoxins could be identified by greater cytotoxicity to rat hepatocytes relative to V79 cells, but that direct-acting hepatotoxins (galactosamine and ethionine) and a group of eight compounds likely to act through interference of basal functions in non-dividing and dividing cells produced similar toxicity in each cell type. It is possible that the greater water-solubility of the direct-acting hepatotoxins relative to the indirect-acting hepatotoxins may contribute to the lack of effect seen with the former group under the conditions of the assay (top concentration of 1 mM).