Guide for performing the mouse lymphoma assay for mammalian cell mutagenicity

Clive, D.; Caspary, William J.; Kirby, Paul E.; Krehl, R.; Moore, Martha M.; Mayo, J K; Oberly, T.J.

doi:10.1016/0165-1218(87)90020-6

Cited by 61 publications

(17 citation statements)

References 22 publications

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“…The Tk target gene used for the MLA is located on mouse chromosome 11 and codes for thymidine kinase (Tk), an enzyme involved in thymidine triphosphate synthesis [49,51] . Thymidine triphosphate can be generated through metabolism of deoxyuridine monophosphate by thymidylate synthetase ( de novo pathway) or by phosphorylation of exogenous thymidine by Tk (pyrimidine salvage pathway).…”

Section: Commonalities and Differences In Protocols For In Vitro Mammmentioning

confidence: 99%

In Vitro Mammalian Cell Mutation Assays

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Moore

Heflich

2007

Preclinical Development Handbook

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Section: Commonalities and Differences In Protocols For In Vitro Mammmentioning

confidence: 99%

In Vitro Mammalian Cell Mutation Assays

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Moore

Heflich

2007

Preclinical Development Handbook

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“…This assay exploits mouse lymphoma cells (L5178Y tk +/− 3.7.2C), heterozygous at the thymidine kinase locus (Tk1) on chromosome 11. Inactivation of the tk + allele (Tk1 b ) induces trifluorothymidine resistance, allowing easy selection of tk −/− mutants (Clive et al, 1987;Nohynek et al, 2004;Isbrucker et al, 2006). MLA can detect a variety of mutations, including point mutations and small mutations within Tk1, losses of Tk1 b or larger deletions including Tk1 b .…”

Section: In Vitro Methods For Genotoxicity Assessmentmentioning

confidence: 99%

Review of current and “omics” methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms

Ouédraogo

Baudoux

Stévigny

et al. 2012

Journal of Ethnopharmacology

124

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“…The assay for forward mutations at the Tk locus of the mouse lymphoma L5178Y (Tk +/− -3.7.2C) cells (referred to as the mouse lymphoma assay, MLA) was developed by Donald Clive and colleagues; [1][2][3] and is one of the most widely used tests in genetic toxicology, second only to the Ames bacterial reverse mutation assay.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Mouse Lymphoma (L5178Y Tk +/− -3.7.2C) Forward Mutation Assay

Schisler

Moore

Gollapudi

2013

Methods in Molecular Biology

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The in vitro mouse lymphoma assay (MLA) is one of the most widely practiced assays in genetic toxicology. MLA detects forward mutations at the thymidine kinase (Tk) locus of the L5178Y (Tk (+/-) -3.7.2C) cell line derived from a mouse thymic lymphoma. This assay is capable of detecting a wide range of genetic events including point mutations, deletions (intragenic) and multilocus, chromosomal rearrangements, mitotic recombination, and nondisjunction. There are two equally accepted versions of the assay, one using soft agar cloning and the second method using liquid media cloning in 96-microwell plates. There are two morphologically distinct types of mutant colonies recovered in the MLA: small- and large-colony mutants. The induction of small-colony mutants is associated with chemicals inducing gross chromosomal aberrations whereas the induction of large mutant colonies is generally associated with chemicals inducing point mutations. The source and karyotype of the cell line as well as the culture conditions are important variables that could influence the assay performance. The assay when performed according to the standards recommended by the International Workshops on Genotoxicity Testing is capable of providing valuable genotoxicity hazard information as part of the overall safety assessment process of various classes of test substances.

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Guide for performing the mouse lymphoma assay for mammalian cell mutagenicity

Cited by 61 publications

References 22 publications

In Vitro Mammalian Cell Mutation Assays

In Vitro Mammalian Cell Mutation Assays

Review of current and “omics” methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms

In Vitro Mouse Lymphoma (L5178Y Tk +/− -3.7.2C) Forward Mutation Assay

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