Ames-positive

A combination of two tests is clearly better than one, but at this early stage, when there is still more chemical development likely, one is probably enough. Given that in silico methods are most effective in the identification or designing out of Ames positive compounds, a single eukaryotic screening test would probably be optimum. 

Figure 8.8 Scaffold (cyclohexene) hierarchy derived from mutagenicity dataP8] The proportion of Ames negative to Ames positive counts is qualitatively indicated below each scaffold. The confidence interval of the proportions is shown on the right of the scaffolds. Data taken from Kho et al.[3 I...

The results of this evaluation are summarized with the statistical parameters sensitivity, the correctly predicted positive compounds, specificity, the correctly predicted negative compounds, and concordance, the correctly predicted positive and negative compounds. In this evaluation 141 out of 225 Ames positive compounds were correctly predicted, which gives a sensitivity of 63% for the system. On the other hand 953 out of 1216 Ames negative compounds were correctly predicted, which gives a specificity of 78 % for the system. The overall concordance, correct positive and correct negative predictions, was 76 %. 

Nitrenium ions formed from a large number of known drugs and Ames positive mutagens were analysed by DFT theory. The lack of a correlation with mutagenicity led to the conclusion that other physical properties besides nitrenium ion stability are important determinants. In a similar paper, energies of the nitrenium ions derived from thousands of commercially available amines were calculated. Contrary to above, the... 

The inhalation toxicity of NF on animals has been studied extensively (37—40). These studies provide the basis of emergency exposure limits (EEL) that have been proposed for NE. The NAS—NRC Committee on Toxicology recommends that the EEL for NE be 10 min at 2250 ppm, 30 min at 750 ppm, and 60 min at 375 ppm. Gaseous NE is considered to be innocuous to the skin and a minor irritant to the eyes and mucous membranes. NE does give a weakly positive metabotically activated Ames test but only at concentrations greater than 2% or 10 times the 10 minute EEL. 

Benzyl chloride induced a positive mutagenic response ia the Ames Assay ia strain TA 100 with and without rat Hver S-9 metaboHc activation. 

Christman, M.F., Morgan,R.W., Jacobson, F.S., Ames, B. (1985). Positive control of a regulon for defenses against oxidative stress and some heat shock proteins in Salmonella typhimurium. Cell 41, 753-762. 

Kitchin KT, Brown JL, Kulkami AP. 1993. Predicting rodent carcinogenicity of Ames test false positives by in vivo biochemical parameters. Mutat Res 290 155-164. 

Ames Laboratory (Iowa State University, USA) investigating new solid state phases based on reduced rare earth halides. Since 1993, she has held a position at the University Jaume 1 of Castello (Spain) and became Associate Professor of Physical Chemistry in 1995. During the second semester of 2005, she held a visiting professor position at the Laboratory of Chemistry, Molecular Engineering and Materials of the CNRS-Universtity of Angers (France). Her research has been focussed on the chemistry of transition metal clusters with special interest in multifunctional molecular materials and the relationship between the molecular and electronic structures of these systems with their properties. She is currently coauthor of around 80 research papers on this and related topics. 

The Ames test involves the reversion from a his— to his+ phenotype in any one of multiple bacterial strains (usually five strains are tested simultaneously). If the addition of test compound to a his— strain of bacteria allows them to grow on histidine deficient media, the obvious conclusion is compound-induced mutagenesis and a high potential hazard for the compound being carcinogenic. This test can also be conducted in the presence or absence of metabolic activation, in order to provide more information on potential risks (i.e., the parent compound may not be mutagenic, but the primary metabolite may present a safety risk). In practice, a positive Ames test almost always leads to discontinuing work on a compound of interest, and so these data are always collected prior to nomination of a compound for development. 

The Ames salmonella-microsome test is a principal sensitive mutagen screening test. Compounds are tested on the mutants of Salmonella typhimurium for reversion from a histidine requirement back to prototrophy. A positive result is seen by the growth of revertant bacteria (which do not require an external histidine source). A microsomal activation system should be included in this assay. The use of five different bacterial test strains are generally required. 

Only two out of 25 Ames-tested organic pigments show a positive result [20],... 

During the mid 1970s the Ames test was headline news in the carcinogenesis community and among regulators. But there was a lot of skepticism - could we really trust such a simple test as a way to identify carcinogens and, perhaps more importantly, could we drop concern for chemicals that failed to give a positive response to his test ... 

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