ALTEX :: Alternatives to Animal Experiments

1994, Volume 3

Genetically Engineered V79 Cell-Lines in Combination with Analytical-Chemical Procedures for Replacing and Refining Animal Experimentation

Johannes Doehmer1 and Jürgen Jacob2

1Institut für Toxikologie und Umwelthygiene der Technischen Universität D-München; 2Biochemisches Institut für Umweltcarcinogene, D-Grobhansdorf

SUMMARY

Since 1986 V79 Chinese hamster cells are being genetically engineered for rat and human enzymes for studies on metabolism dependent effects in toxicology and pharmacology under defined conditions. The metabolic activation of potentially harmful chemicals is of interest in toxicology, because metabolites may have their own toxic potency. Anabolic and catabolic pathways of drugs are of interest in pharmacology, because metabolism has a decisive impact on the efficacy of drugs. As an example for the usefulness of V79 cells genetically engineered for metabolic competence, and their advantage over animal experimentation, metabolic activation of polycyclic aromatic hydrocarbons has been studied. Comparative studies using V79 cells expressing rat and human enzymes revealed striking differences in the metabolite profile, which made evident, that human beings are at more risk than the rat, when exposed to polycyclic aromatic hydrocarbons. This suggests at the same time, that results obtained from animal experimentation are to be treated with caution, if they form the basis for risk assessment.

Keywords: V79 cells, cytochromes P450, xenobiotics