Significance of Various Enzymes in the Control of Mutagenic and Carcinogenic Metabolites Derived from Aromatic Structures*

One important early contribution to the control of chemical carcinogenesis i s provided by the enzyme pattern responsible for the generation and disposition of reactive metabolites. Especially well studied i s the important group of en-zymes 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 wi l l 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 controllin