Genotoxicity testing assays

Kado NY, PA Kuzmicky, G Loarca-Pina, MM Mumtaz (1998) Genotoxicity testing of methyl tertiary-butyl ether (MTBE) in the Salmonella microsuspension assay and mouse bone marrow micronucleus test Mut Res 412 131-138. 

Environment Canada recently developed an evaluation system based on effluent toxicity testing, capable of ranking the environmental hazards of industrial effluents [185]. This so-called Potential Ecotoxic Effects Probe (PEEP) incorporates the results of a variety of small-scale toxicity tests into one relative toxicity index to prioritize effluents for sanitation. In the index no allowance has been made for in-stream dilution, therefore the acmal risk for environmental effects is not modeled. The tests performed on each effluent are the following bacterial assay [V.fisheri (P. phosphoreum), Microtox], microalgal assay S. capricornutum) crustacean assay (C. dubiay, and bacterial genotoxicity test E. coli, SOS-test). 

Results of genotoxic tests have been mixed. In general hydroxylamine and its salts have shown positive results in in vitro assays and negative results in in vivo mammalian assays." ... 

The first level of genotoxicity testing likely to be used in the near future is hit profiling. For numerical reasons, hits from a discovery campaign can be considered alongside smaller complete libraries of natural products and specialist collections enriched for particular target types (inhibitors of kinases, proteases, HDACs, etc.). All would benefit from the early inclusion of genotoxicity data in the profile. Of the assays... 

In general, genotoxicity standard assays (e.g., bacterial reverse mutation assay [Ames test], in vitro chromosomal aberration assay, mouse lymphoma gene mutation assay, and rodent micronucleus assay) may not be suitable assays because the test cells do not contain the appropriate receptors to transport the product (i.e.,not a relevant species) or because the biopharmaceutical... 

Salmonella typhimurium/ Escherichia coli Plate Incorporation Mutation Assay in the Presence and Absence of Induced Rat Liver S-9 ICH S2A Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals, ICH S2B Genotoxicity A Standard Battery of Genotoxicity Testing of Pharmaceuticals 2-A 4-6 10,000-15,000... 

Other in vivo somatic cell genotoxicity tests which are supported by positive results from in vitro mutagenicity assays. 

Ammonium perchlorate was tested in a battery of genotoxicity tests and found to be negative in all tests, including a reverse mutation assay in Salmonella typhimurium and the L5178Y/TK" mouse Ecotoxicology... 

Moore MM, Honma M, Clements J, et al. (2002) Mouse lymphoma thymidine kinase gene mutation assay followup International Workshop on Genotoxicity Test Procedures, New Orleans, Louisiana, April 2000. Environmental and Molecular Mutagenesis 40(4) 292-299. 

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