Metabolic activation of drugs in mutagenicity tests in vitro.

The metabolic pathways of chemical compounds of pharmaceutical interest are reviewed in relation to the role of activation and detoxification in the process of mutagenicity. The properties and subcellular localization of the enzymes involved are given together with the main reactions they catalyze. The role of metabolism in mutagenicity testing in vitro is discussed with special emphasis on the choice of the enzymatic system. Parameters such as species, strain, sex, diet, and induction are considered. The effect of various enzymatic effectors added in vitro is also discussed. It is concluded that the metabolism of drugs is very complex, involving both activation and detoxification processes catalyzed by a large variety of enzymes. Production of mutations in vitro in prokaryotic or eukaryotic cells is the results of a balance between all those pathways. Metabolic activation thus merits special attention.