Methods for analysis of the mutagenicity of indirect mutagens/carcinogens in eukaryotic cells

The review discusses the variety of methods for activation of indirect mutagens/carcinogens and testing them in cell cultures, especially in mammalian cell cultures. After the necessity for including metabolizing components in mutagenicity tests has been pointed out, the enzymes that transform foreign compounds metabolically, and the factors influencing them, are described. In the main section the various methods of activating indirect mutagens/carcinogens are presented. The methods of including in vivo metabolism in mutagenicity tests are: Analysis of cells from organisms contaminated with a chemical (III.1.a); body fluid-mediated mutagenesis (III.1.b); host-mediated assay (III.1.c). The following activation systems are suitable for including in vitro metabolism of test compounds in mutagenicity tests: Liver and lung perfusion (III.2.a.α); organ slices and homogenates (III.2.a.β); subcellular fractions (III.2.a.γ); cultivated cells (cell-mediated mutagenesis) (III.2.b); nonenzymatic activation systems (III.2.c). Finally the main factors that influence the metabolism of test substances are summarized. Two figures illustrate the mutagenicity tests with regard to the metabolism of mammalian livers and the methods of performing mutagenicity tests in man.