Advanced Approaches to Model Xenobiotic Metabolism in Bacterial Genotoxicology In Vitro.
During the past 30 years there has been considerable progress in the development of bacterial test systems for use in genotoxicity testing by the stable introduction of expression vectors (cDNAs) coding for xenobiotic-metabolizing enzymes into bacterial cells. The development not only provides insights into the mechanisms of bioactivation of xenobiotic compounds but also evaluates the roles of enzymes involved in metabolic activation or inactivation in chemical carcinogenesis. This review describes recent advances in bacterial genotoxicity assays and their future prospects, with a focus on the development and application of genetically engineering bacterial cells to incorporate some of the enzymatic activities involved in the bio-activation process of xenobiotics. Various genes have been introduced into bacterial umu tester strains encoding enzymes for genotoxic bioactivation, including bacterial nitroreductase and O-acetyltransferase, human cytochrome P450 monooxygenases, rat glutathione S-transferases, and human N-acetyltransferases and sulfotransferases. Their application has provided new tools for genotoxicity assays and for studying the role of biotransformation in chemical carcinogenesis in humans.
Institute of Life and Environmental Sciences, Osaka Shin-Ai College, 6-2-28 Tsurumi, Tsurumi-ku, 538-0053, Japan. oda.1948@hotmail.com.
Yoshimitsu
Y
Oda
D001419:Bacteria / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D005544:Forecasting; D005818:Genetic Engineering / Q000379:methods / Q000639:trends; D009152:Mutagenicity Tests / Q000379:methods / Q000639:trends*; D009153:Mutagens / Q000633:toxicity*; D011995:Recombination, Genetic / Q000235:genetics; D013045:Species Specificity; D015262:Xenobiotics / Q000378:metabolism*
D009153:Mutagens; D015262:Xenobiotics
Bacterial recombinant tester strain; Genotoxicity; Metabolic activation; Mutagenicity; SOS response; Xenobiotic metabolism; umu test