TY - JOUR
T1 - Symposium overview
T2 - Characterization of xenobiotic metabolizing enzyme function using heterologous expression systems
AU - Townsend, A. J.
AU - Kiningham, K. K.
AU - St. Clair, D.
AU - Tephly, T. R.
AU - Morrow, C. S.
AU - Guengerich, F. P.
PY - 1999
Y1 - 1999
N2 - Genetically modified cell lines can be very useful models for assessing the toxicologic effects of modulation of expression of individual gene products in comparison to their isogenic parental control cell lines. This symposium begins with an overview of general issues related to development and utilization of model systems created by transfection of cell lines to induce elevated expression of metabolic enzymes of toxicologic relevance. Selected studies that illustrate the heterologous expression rationale and various approaches to transgenic-cell model construction are represented. Results to date with cells engineered to express specific transfected genes are discussed, with emphasis on the effects of expression of selected phase I or phase II enzymes on cellular sensitivity to several toxic end-points. The individual sections highlight the utility of these model cell lines for examining the role of enzyme catalysis and function in metabolism of biologically active xenobiotic or endobiotic compounds of interest in toxicology. Both activating and detoxifying enzymes are discussed, with principal emphasis on the latter. This symposium includes talks on transfected cells that express aldehyde dehydrogenases, superoxide dismutase, UDP-glycosyltransferases, glutathione transferases, and cytochrome P450 isozymes. In addition to the general toxicologic utility and advantages of these genetically engineered cell lines, this overview emphasizes their particular contributions to the insights obtained to date with the specific model cell lines.
AB - Genetically modified cell lines can be very useful models for assessing the toxicologic effects of modulation of expression of individual gene products in comparison to their isogenic parental control cell lines. This symposium begins with an overview of general issues related to development and utilization of model systems created by transfection of cell lines to induce elevated expression of metabolic enzymes of toxicologic relevance. Selected studies that illustrate the heterologous expression rationale and various approaches to transgenic-cell model construction are represented. Results to date with cells engineered to express specific transfected genes are discussed, with emphasis on the effects of expression of selected phase I or phase II enzymes on cellular sensitivity to several toxic end-points. The individual sections highlight the utility of these model cell lines for examining the role of enzyme catalysis and function in metabolism of biologically active xenobiotic or endobiotic compounds of interest in toxicology. Both activating and detoxifying enzymes are discussed, with principal emphasis on the latter. This symposium includes talks on transfected cells that express aldehyde dehydrogenases, superoxide dismutase, UDP-glycosyltransferases, glutathione transferases, and cytochrome P450 isozymes. In addition to the general toxicologic utility and advantages of these genetically engineered cell lines, this overview emphasizes their particular contributions to the insights obtained to date with the specific model cell lines.
KW - Aldehyde dehydrogenase
KW - Cell culture cytotoxicity
KW - Cytochrome P-450
KW - Genotoxicity
KW - Glutathione S- transferases
KW - Heterologous expression
KW - Superoxide dismutase
KW - Transgenic cell models
KW - UDP-glycosyltransferases
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UR - http://www.scopus.com/inward/citedby.url?scp=0032933038&partnerID=8YFLogxK
U2 - 10.1093/toxsci/48.2.143
DO - 10.1093/toxsci/48.2.143
M3 - Article
C2 - 10353304
AN - SCOPUS:0032933038
SN - 1096-6080
VL - 48
SP - 143
EP - 150
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 2
ER -