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RESEARCH PRODUCT

Importance of Individual Enzymes in the Control of Ultimate Carcinogens

subject

description

The metabolic activation of most chemical mutagens and carcinogens is a prerequisite for their mutagenic and carcinogenic activity. Reactive metabolites are under the control of activating, inactivating and precursor sequestering enzymes. These enzymes are under the long-term control of induction and repression and under the short-term control of posttranslational modification. As far as carcinogen-metabolizing enzymes are concerned, posttranslational modification has received little attention. This short-term regulation may be especially important since it works fast and may affect the enzymatic activity as well as the degradation of the enzyme. The enzymatic activity is modified by activators and inhibitors. Further crucial determinants of the control of ultimate carcinogens are the compartmentalization of these enzymes and of the target molecules. Carcinogen metabolizing enzymes differ widely between toxicological test systems, animal species and man. Careful consideration of the basic mechanisms responsible for the control of the ultimately active species derived from mutagenic tumor initiators is important, since due to the long latency time of genotoxic effects correct predictions of genotoxic risks are urgently needed.