Mouse Lymphoma Test

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

Mouse lymphoma test in mouse lymphoma cells (in vitro) Micronucleus test in rodent bone marrow (in vivo)... 

Ames Salmonella and mouse lymphoma tests for mutagenicity have been negative. 

The micronucleus assay is one type of study recommended by the FDA Redbook and ICH guidelines as part of a standard genetic toxicology battery. The other assays include the Ames (bacterial reverse mutation) and mouse lymphoma tests. 

Studies of sister chromatid exchange have been positive, Ames Salmonella tests have been negative, mouse lymphoma tests have been negative, and Chinese hamster ovary assays have been negative for mutagenicity. 

Mammalian cell Mouse lymphoma test Gene mutations 476 870.5300... 

No evidence of mutagenicity or clastogenicity of extracts of hawthorn leaf and flower were observed using standard tests, including the Ames test, the mouse micronucleus assay, the mouse lymphoma test, and the human lymphoma test (Schlegelmilch and Heywood 1994). 

Genotoxicity tests were performed with senna fruit, senna leaf extract, sennosides, rhein, and aloe-emodin. Senna fruit, sennosides, and rhein did not increase mutation frequencies in the following test systems bacterial systems, mammalian cell culture tests, mouse lymphoma test, chromosome aberration test with Chinese hamster ovary (CHO) cells, bone marrow micronucleus test, chromosome aberration tests, and melanoblast cell test. With aloe-emodin, mutagenic effects were observed only in vitro in the chromosome aberration test with CHO cells and in the Salmonella reverse mutation test. In the in vitro gene mutation test with V79 cells, no mutagenic potential of aloe-emodin was observed. In vivo studies indicated no mutagenic activity of aloe-emodin, and aloe-emodin did not induce unscheduled DNA synthesis in an ex vivo assay performed with hepato-cytes of male rats (Heidemann et al. 1993). 

The mouse lymphoma test uses a mutated mouse cancer cell line in which a partially damaged gene exists. When this gene is completely damaged, this mutated cell line is able to survive and replicate in the presence of a particular chemical. The cells are incubated within that chemical after exposure to the test article. If an increase in viability is detected, it would indicate that the test article was able to inactivate totally or damage the gene. 

Mammalian cell gene mutation test (mouse lymphoma test) Mammalian cell Gene mutations B17/TG476... 

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

Garner RC, Campbell J. 1985. Tests for the induction of mutations to ouabain or 6-thioguanine resistance in mouse lymphoma L5178Y cells. In Ashby J, de Serres FJ, et al., eds. Progress in mutation research. Vol. 5. Evaluation of short-terms tests for carcinogens. Amsterdam, The Netherlands Elsevier Science Publishers, 525-529. 

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. 

Brusick and Matheson (1976) reported that 1,1-dimethylhydrazine failed to increase reversions in Salmonella typhimurium or Saccharomyces cerevisiae gene mutation assays with or without metabolic activation. A concentration-related response was observed in the mouse lymphoma assay (with activation). Dominant lethal tests were negative. 

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. 

The mouse lymphoma forward mutation test at the thymidine kinase locus (detects mutations to a nonfunctional thymidine kinase in a line of culture mouse lymphoma cells). 

In a battery of mutagenicity and genotoxicity studies, PGDN tested negative except in L5178Y mouse lymphoma cells where it induced mutations at... 

In vitro mammalian cell test (chromosome aberration test or mouse lymphoma assay)... 

Two main protocols have been devised for carrying out mutation assays with mouse lymphoma L5178Y cells, plating the cells in soft agar or a fluctuation test approach. The latter is described in the following section, based on Cole et al. (1986). The reader is referred to Clive et al. (1987) for a full description of the soft-agar method. 

In Vitro Mammalian Cell Gene Mutation Test (Using Mouse Lymphoma... 

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. 

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. 

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