Mouse lymphoma tk test

Detection of chromosomal damage using in vitro method (mouse lymphoma tk test, a test to evaluate the potential of a drug to cause mutations to thymidine kinase [tk])... 

In vitro assays are increasingly being used. Some of the reasons are cost, availability of more rapid results, and avoidance of negative publicity. Assays such as cytochrome P-450 enzymes, the Ames test, and the mouse lymphoma tk test are in vitro methods. For absorption studies, Caco-2 (Exhibit 5.9) and Madin-Darby canine kidney cell assays are now routinely used. Hepatocyte cell lines with metabolism capacity are being developed to test drug metabolism and toxicity. All these examples show that, where possible, pharmaceutical firms are gradually dispensing with animal studies. 

Chromosomal aberration test Mouse lymphoma TK test Cross reactivity study... 

An in-vitro test with mammalian cells (chromosomal damage or mouse lymphoma tk assay)... 

An in vitro cytogenetic test in mammahan cehs or in vitro mouse lymphoma tk + assay. 

It is acceptable to select the mouse lymphoma tk instead of chromosomal aberration test with mammalian cells. 

Matheson et al. (1978) reported the results of a battery of in vivo and in vitro assays to assess the genotoxicity of 1,1-dimethylhydrazine. Included were the Ames Salmonella microsome assay, a microbial suspension assay, mutation induction at the TK locus in L5178Y mouse lymphoma cells, stimulation of UDS in WI-38 cells, and a dominant lethal assay in mice. 1,1-Dimethylhydrazine was active in all of the tests except the dominant lethal assay. 

Under Guideline S2B, the following standard test battery is recommended (1) a test for gene mutation in bacteria, (2) an in vitro test with cytogenetic evaluation of chromosomal damage with mammalian cells or an in vitro mouse lymphoma thymidine kinase (TK) assay, and (3) an in vivo test for chromosomal damage using rodent hematopoietic cells. 

In Vitro Mammalian Cell Gene Mutation Test (Using Mouse Lymphoma L5178Y TK+/- Cells)... 

Myhr, B.C., Bowers, L.R. Caspaiy, W.J. (1986) Results from the testing of coded chemicals in the L5178Y TK+ mouse lymphoma mutagenesis assay. Environ, mol. Mutagen., 7 (Suppl. 3), 58... 

A typical test system is the analysis of the TK locus in mouse lymphoma cells for mutations that confer resistance to bromodeoxyuracil. The tests are conducted with and without the S-9 fraction from induced rat liver because the lymphoma cells have little activating ability. Both positive and negative controls are included, and the parameter... 

One system uses mouse lymphoma cells and detects mutations that cause deficiency of thymidine kinase (TK). Another uses Chinese hamster cells and detects mutations in the gene that produces hypoxanthine-guanine phosphoribosyl transferase (HGPRT). Both tests cure efficient, are widely applied, and can be completed in a few weeks. Although not as simple, rapid, and efficient as the Salmonella tests, they have the advantage of being done in a eukaryote. Mammalian-cell cultures cure also used to test for chromosomal mutation. 

What is the potential of a test article with and without metabolic activation to induce forward mutations at the thymidine kinase locus of L5178Y TK+/-mouse lymphoma cells ... 

L5178Y tk+/— mouse lymphoma test MLA Chromosome aberrations Point mutations and structural alterations, based on mutations in the tk gene... 

An in-vitro test with cytogenetic evaluation of chromosomal damage with mammalian cells or an in-vitro mouse lymphoma thymidine kinase (tK) assay... 

Hydroquinone was not mutagenic in Salmonella typhimurium strains with or without exogenous metabolic activation. It induced trifluorothymidine resistance in mouse L5178Y/TK lymphoma cells in the presence or absence of metabolic activation. An equivocal response was obtained in tests for induction of sex-linked recessive lethal mutations in Drosophila administered hydroquinone by feeding. Hydroquinone induced sister chromatid exchanges in Chinese hamster ovary cells with or without exogenous metabolic activation and caused chromosomal aberrations in the presence of activation. 

Isophorone induced sister chromatid exchanges but not chromosome aberrations in Chinese hamster ovary cells. Isophorone was positive in L5178Y tk- -/tk — mouse lymphoma cell forward mutation assay without metabolic activation. Isophorone was negative in tests with Salmonella typhimurium bacterial strains... 

Alosetron was not genotoxic in the Ames tests, the mouse lymphoma cell (L5178Y/TK +) forward gene mutation test, the human lymphocyte chromosome aberration test, and the rat hepatocyte unscheduled DNA synthesis test. Nonmutagenic in the rat micronucleus assay. 

The mouse lymphoma (MOLY) assay is an in vitro mammalian cell gene mutation test that can be used to detect gene mutations induced by chemical substances. The cell line used is the L5178Y MOLY cell. In these cell lines the most commonly used genetic end points measure mutation at the thymidine kinase (TK) locus on the mouse chromosome 11b. 

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