[Primary cultures of rat hepatocytes on microcarriers as a metabolising system in toxicity testing in cell cultures]

The toxicity of many chemicals is modified by biotransformation reactions in the liver. To detect metabolism-mediated alterations of the cytotoxicity of chemicals in vitro, a coculture system consisting of rat hepatocytes on collagen-coated microcarriers and "monolayers" of BALB/c3T3 cells was developed. This cocultivation system was used to study toxic effects of three model compounds, i.e. cyclophosphamide, allyl alcohol and ethylene glycol, respectively. Cytotoxicity to 3T3 cells for each compound increased in cocultures with hepatocytes. The parallel assessment of toxicity to both cell types in coculture and to cultures of 3T3 cells revealed qualitatively as well as quantitatively different toxic effects of these substances. The results indicate that cocultivation of microcarrier-attached hepatocytes with target cells could represent valuable tool to study effects of biotransformation on the toxicity of xenobiotics in vitro.