PMID: 6398501Jan 1, 1984Paper

Significance of various enzymes in the control of mutagenic and carcinogenic metabolites derived from aromatic structures

Toxicologic Pathology
F Oesch

Abstract

One important early contribution to the control of chemical carcinogenesis is provided by the enzyme pattern responsible for the generation and disposition of reactive metabolites. Especially well studied is the important group of enzymes responsible for the control of reactive epoxides. Many natural as well as man-made foreign compounds, including pharmaceuticals, possess olefinic or aromatic double bonds. Such compounds can be transformed to epoxides by microsomal monooxygenases present in very many mammalian organs. By virtue of their electrophilic reactivity such epoxides may spontaneously react with nucleophilic centers in the cell and thus covalently bind to DNA, RNA, and protein. Such alterations of critical cellular macromolecules may disturb the normal biochemistry of the cell and lead to cytotoxic, allergenic, mutagenic, and/or carcinogenic effects. Whether such effects will be manifested depends on one hand on the chemical reactivity as well as other properties (geometry, lipophilicity) of the epoxide in question. On the other hand, enzymes controlling the concentration of such epoxides are another important contributing factor. Several microsomal monooxygenases exist differing in activity and substrate specificity. ...Continue Reading

References

Apr 1, 1975·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J BoothP Sims
Jul 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·A W WoodA H Conney
Dec 30, 1977·Archives of Toxicology·R E Lehr, D M Jerina
Feb 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·E HubermanV Gelboin
Apr 1, 1975·Journal of Cellular Physiology·D W NebertA P Poland
Nov 15, 1975·FEBS Letters·P Bentley, F Oesch
Jan 1, 1974·Advances in Cancer Research·P Sims, P L Grover
Aug 16, 1974·Science·D M Jerina, J W Daly

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Citations

Aug 1, 1987·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·J P Whitty, L F Bjeldanes
Sep 14, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Rosanna RinaldiRalf Morgenstern

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