TK locus

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 L5178Y mouse lymphoma assay (MLA) for mutants at the TK locus. 

That the aromatic amine benzidine is mutagenic only at the TK locus in L5178Y TK+,/ cells. The most disturbing finding was that benzidine (detectable without metabolism by S9 mix) did not produce detectable DNA adducts (as shown by 32P-post-labeling) in L5178Y cells. Thus, the mechanism... 

Clive, D. and Spector, J.F.S., Laboratory procedure for assessing specific locus mutations at the TK locus in cultured L5178Y mouse lymphoma cells, Mutat. Res., 31, 17, 1975. 

Clive D. 1977. A linear relationship between tumorigenic potency in vivo and mutagenic potency at the heterozygous thymidine kinase (TK+/-) locus of L5178Y mouse lymphoma cell coupled with mammalian metabolism. Dev Toxicol Environ Sci 2 241-247. 

A variety of mammalian cell culture systems can be used to detect mutations induced by chemical substances. The L5178Y mouse l)nnphoma line, measuring mutation at the TK locus, is preferred. TK is an important enz)une involved in DNA synthesis. Cells are exposed to the test substance at various concentrations, in the presence and absence of a metabolic activation system, for a suitable period of time, and then subcultured to assess cytotoxicity and to allow phenotypic expression prior to mutant selection. Cells deficient in TK because of a forward mutation are resistant to the cytotoxic effects of pyrimidine analogues (antimetabolites), such as trifluorothymidine (TFT). This is because the antimetabolites cannot be incorporated into cellular nucleotides and kill the cell through inhibition of cellular metabolism. After treatment, cells are grown in a medium containing TFT mutant cells can proliferate in the presence of TFT, whereas normal cells containing TK are killed. This allows the detection of an increase in mutant... 

DNA single-strand breaks were not induced by di(2-ethylhexyl) phthalate in primary cultures of rat or Syrian hamster hepatocytes or in Chinese hamster ovary (CHO) cells. Unscheduled DNA s5uithesis was not induced in rat or mouse primary hepatocytes exposed to di(2-ethylhexyl) phthalate. Only one of six studies reported induction of gene mutations at the Tk locus in mouse l5unphoma L5178Y cells exposed to di(2-ethylhexyl) phthalate in the absence of an exogenous metabolic activation system. Ouabain-resistant mutants were not induced in mouse lymphoma or BALB/c-3T3 cells. 

Gene mutation, L5178Y cells, Tk locus in vitro, forward mutation - - 1000 McGregor et a/. (1988)... 

Gene mutation, mouse lymphoma L5178Y cells, Tk locus in vitro... 

Diethanolamine did not induce mutations in mouse lymphoma L5178Y cells at the Tk locus in the presence or absence of exogenous metabolic activation in one study. It did not induce sister chromatid exchanges in Chinese hamster ovary cells in two studies with or without exogenous metabolic activation. A single study using cultured rat liver cells found no induction of chromosomal aberrations and one study in Chinese hamster ovary cells also found no induction of chromosomal aberrations in either the presence or absence of exogenous metabolic activation. 

Mutation, mouse lymphoma, L5178Y cells Tk locus in vitro + NT 0.0625 National Toxicology Program (1993)... 

GST, Gene mutation, mouse lymphoma LS178Y cells, tk locus in vitro + + 40 Amacher Turner (198S)... 

GIH, Gene mutation, human lymphoblastoid TK6 cells tk locus in vitro - (+) 74 Recio Skopek (1988)... 

Ross, C.A. McGregor, D.B. (1982) Mutation at the TK locus of mouse lymphoma L5178Y cells by 4CMB, 4HMB and BC. Mutat. Res., 100, 249-251... 

Phenol induced mutations at the hprt locus of Chinese hamster V79 cells in the presence of an exogenous metabolic system from the livers of phenobarbital-induced mice and tk locus mutations in mouse lymphoma L5178Y cells in the presence or the absence of an exogenous metabolic activation system. Micronuclei were induced by phenol in Chinese hamster ovary cells in one study and sister chromatid exchanges in mammalian cells were increased in several studies, including three with human lymphocytes. 

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