Short-term and long-term modulation of the enzymatic control of mutagenic and carcinogenic metabolites.

Many mutagenic and carcinogenic metabolites are controlled by several enzymes including activating, inactivating and precursor-sequestering enzymes. These enzymes themselves are, in turn, also subject to control which, usually, is also multiple, including enzyme induction, repression, activation and inhibition. For several classes of chemicals strong influences of such enzyme modulations on the mutagenicity have been elucidated. The effects of modulation of individual enzymes contributing to the control of a given mutagenic metabolite can be mutually antagonistic or potentiating and can markedly differ in their time frame, ranging from very short-term to extremely long-term modulation. Therefore, the complex interaction between all these modulations must be considered when evaluating the enzymatic control of mutagenic metabolites.