Point mutation tests

Some dyes exhibit a mutagenic potential. The Ames test is commonly used as a first screening for the prediction of mutagenicity of a substance. It is a bacterial point mutation test inducing activity, which uses special strains of the bacteria Salmonella typhimurium with growth-dependence on the amino acid histidine. The dose-dependent reversion to histidine-independent growth is the marker for a point mutation. 

Point mutation tests have been developed also for cultured mammalian cells (de Marini et al, 1989). These tests are based on the mutational resistance to otherwise cytotoxic agents (i.e. TKor HPRT mutations, conferring resistance to trifluorothymidine and 6-thioguanine, respectively). Compared to the Ames test and other bacterial assays they are, however, more laborious and time consuming. 

Imidacloprid has been evaluated for mutagenicity using a full complement of in vitro and in vivo tests required for registration. All tests, including the in vitro point mutation tests, in vivo chromosomal aberration tests, a mitotic recombination test in yeast, a rec assay with Bacillus subtilis, and the unscheduled DNA synthesis (UDS), were negative. 

In tests with rabbits non-irritant on the skin, mild irritant at the eyes. A skin sensitizer according to the guinea pig test. In tests with rats non-teratogenic and non-embryotoxic. Ames test negative. Micronucleus test non-geno-toxic. V 79 point mutation test, DNA repair (human fibroplasts) non-mutagenic. 

Amacher, D.E., S C Pail lei. G.N.Tumer, V.A.Ray, and D.S.Salsburg. 1980. Point mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells. II. Test validation and interpretation. Mutat. Res. 72 447-474. 

The Ames Salmonella typhimurium microsome reverse mutation test (ability to produce point gene mutations of a base pair). 

KLOSE, J., Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues. A novel approach to testing for induced point mutations in mammals, Humangenetik, 1975, 26,231-243. 

The test is commonly employed as an initial screen for genotoxic activity and, in particular, for point mutation-inducing activity. It detects point mutations, which involve substimtion, addition or deletion of one or a few DNA base pairs. The reverse mutation test in either Salmonella typhimurium or Escherichia coli detects mutation in an amino acid requiring strain (histidine or tryptophan, respectively) to produce a strain independent of an outside supply of amino acid. The principle of the test is that it detects mutations, which revert mutations present in the test strains and restore the functional capability of the bacteria to synthesize an essential amino acid. The revertant bacteria are detected by their ability to grow in the absence of the amino acid required by the parent test strain. 

Positive results from the bacterial reverse mutation test (often referred to as the Ames test) indicate that a substance induces point mutations by base pair substimtion or frameshift in the... 

Positive results from the gene mutation test in Aspergillus nidulans indicate that the test substance causes gene (point) mutations in the DNA of this organism caused by base pair changes and small deletions in the genome. 

AG 1024 has been extensively studied as an IGFR inhibitor [70] and is a substrate competitive inhibitor of this kinase [71]. AG1024 also inhibits other kinases including c-Kit [72]. Additional studies will be needed, including a direct measurement of Abl activity and possible subsequent testing against the imatinib resistant Abl point mutations, to ascertain the possible therapeutic utility of AG 1024. 

Ecoflex (powder) was tested for its mutagenic potential on the basis of its ability to induce point mutations in several bacterial strains Salmonella typhimurium and Escherichia coll) in a reverse mutation assay (Ames test), according to OECD guideline 471. Results revealed that the polyester is not mutagenic to bacteria. 

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