Genetically engineered bacteria for genotoxicity assessment

Ever since the introduction of the Salmonella typhimurium mammalian microsome mutagenicity assay (the Ames test) over three decades ago, there has been a constant development of additional genotoxicity assays based upon the use of genetically engineered microorganisms. Such assays rely either on reversion principles similar to those of the Ames test or on promoter-reporter fusions that generate a quantifiable dose-dependent signal in the presence of potential DNA damaging compounds and the induction of repair mechanisms. While some of these assays were only briefly described in the scientific literature, others have been developed all the way to commercial products. Out of these, only one, the umu-test has been fully validated and ISO- and OECD-standardized. Herein we review the main directions undertaken in the construction and testing of bacterial-based genotoxicity bioassays, including the attempts to incorporate at least a partial metabolic activation capacity into the molecular design. We list the genetic modifications introduced into the tester strains, compare the performance of the different assays, and briefly describe the first attempts to incorporate such bacterial reporters into actual genotoxicity testing devices.