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Toxicological Implications of Enzymatic Control of Reactive Metabolites

Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-6500 Mainz, FRG

J. Doehmer

Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-6500 Mainz, FRG

T. Friedberg

Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-6500 Mainz, FRG

H.R. Glatt

Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-6500 Mainz, FRG

B. Oesch-Bartlomowicz

Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-6500 Mainz, FRG

K.L. Platt

Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-6500 Mainz, FRG

P. Steinberg

Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-6500 Mainz, FRG

D. Utesch

Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-6500 Mainz, FRG

H. Thomas

Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-6500 Mainz, FRG

Many foreign compounds are transformed into reactive metabolites, which may produce genotoxic effects by chemically altering critical biomolecules. Reactive metabolites are under the control of activating, inactivating and precursor sequestering enzymes. Such enzymes are under the long-term control of induction and repression, as well as the short-term control of post-translational modification and low molecular weight activators or inhibitors. In addition, the efficiency of these enzyme systems in preventing reactive metabolite-mediated toxicity is directed by their subcellular compartmentalization and isoenzymic multiplicity. Extrapolation from toxicological test systems to the human requires information of these variables in the system in question and in man. Differences in susceptibility to toxic challenges between species and individuals are often causally linked to differences in these control factors.

Human & Experimental Toxicology, Vol. 9, No. 3, 171-177 (1990)
DOI: 10.1177/096032719000900309


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