Symposium overview: Characterization of xenobiotic metabolizing enzyme function using heterologous expression systems

Genetically modified cell lines can be very useful models for assessing the toxicologic effects of modulation of expression of individual gene product s in comparison to their isogenic parental control cell lines. This symposi um begins with an overview of general issues related to development and uti lization of model systems created by transfection of cell lines to induce e levated expression of metabolic enzymes of toxicologic relevance. Selected studies that illustrate the heterologous expression rationale and various a pproaches to transgenic-cell model construction are represented. Results to date with cells engineered to express specific transfected genes are discu ssed, with emphasis on the effects of expression of selected phase I or pha se II enzymes on cellular sensitivity to several toxic end-points. The indi vidual sections highlight the utility of these model cell lines for examini ng the role of enzyme catalysis and function in metabolism of biologically active xenobiotic or endobiotic compounds of interest in toxicology. Both a ctivating and detoxifying enzymes are discussed, with principal emphasis on the latter. This symposium includes talks on transfected cells that expres s aldehyde dehydrogenases, superoxide dismtase, UDP-glycosyltransferases, g lutathione transferases, and cytochrome P450 isozymes. In addition to the g eneral toxicologic utility and advantages of these genetically engineered c ell lines, this overview emphasizes their particular contributions to the i nsights obtained to date with the specific model cell lines.