Genotoxicity of chemical compounds

Toxicol., 18, 1071-1080 (2005). Prediction of Genotoxicity of Chemical Compounds by Statistical Learning Methods. 

The Ames test is thus typically a bacterial test to assess the genotoxicity of chemicals or environmental compounds but it can be used also to detect the presence of mutagens (and hence reflect a mutagen exposure) in human body fluids, especially in the urine. The Ames test thus can be used as a tool for human biomonitoring studies as well. 

Clearly, for some endpoints the models are more reliable. This is due to the higher number of compounds available to build up the model and to the complexity of the toxicological process which is modeled. Thus, for instance, models for genotoxicity can refer to many thousands of chemicals with experimental values, and the process is relatively simple. Conversely, reproductive toxicity is a much more complex endpoint and the number of chemicals with experimental data is limited (a few hundreds). 

One especially successful method of testing complex mixtures is bioassay-directed fractionation followed by chemical identification of active compounds. Until now this method has mainly been used for the testing and identification of genotoxic compounds in environmental mixtures such as extracts of air particulates, exhaust condensates, and cooked foods. In this approach, each fraction is bioassayed untd the major class of specihc chemical(s) responsible for the activity can be isolated and chemically characterized, which make a risk assessment of the mixture possible. 

Excerpt 4D is from Chemical Research in Toxicology. The authors investigate the genotoxicity of three different chromium (Iff) compounds (chromium chloride,... 

The NIH set up a Chemical Genomics Center (NCGC) in 2007 to reproduce the facilities found in the best of the pharmaceutical company screening programs. NCGC runs a variety of tests at 15 dilutions from a highest concentration of about 92 J,M and, in the examples above, this would detect the genotoxicity of the most potent compounds, but not the least potent - and most likely irrelevant positive results. 

Only recently have N -nitroso Amadori compounds been characterized chemically. The first description of an -nltroso derivative of an Amadori compound reported the formation of 1-deoxy-l-(N -nitroso-3,4-xylidino)-D-f ructose to confirm that a secondary amino group had been formed in an Amadori compound ( 6). Coughlin et al. ( 7) and Heyns et al. ( 8) described the formation of nitrosated Amadori compounds. Since Amadori compounds are weakly basic secondary amines and occur widely in Maillard browned foods and beverages ( 5) and unburned tobacco ( ), the genotoxic potential of these compounds is of interest. 

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