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Updated: Aug 17, 2026
Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
Published on: February 24, 2014
Methyl methanesulphonate mutagenesis in L5178Y mouse lymphoma cells
Abstract:
The alkylating agent MMS was toxic to mouse lymphoma L5178Y cells and decreased their growth rate. A dose-dependent induction of thioguanine- and thymidine- but not ouabain-resistant variants was observed. The prolonged period for expression of thioguanine-resistant variants observed with other mutagens was also found in these studies. A comparison of MMS and EMS showed that MMS on a molar basis was approximately 10 times more toxic than EMS. With mutation, however, when evaluated at equal levels of cell killing MMS and EMS induced the same number of thymidine-resistant variants. For thioguanine-resistant variants MMS was approximately 10-fold less efficient than EMS, while for ouabain-resistance MMS, unlike EMBS, produced no variants at all. The ouabain results were further compared with positive results obtained using a modified Luria--Delbrück fluctuation test.
Insights
Methyl methanesulfonate (MMS) is toxic to mouse lymphoma cells and induces mutations. MMS is more toxic than ethyl methanesulfonate (EMS), but both induce similar thymidine resistance, while EMS is more efficient at inducing thioguanine resistance.
Area of Science:
- Toxicology
- Mutagenesis
- Cell Biology
Background:
- Alkylating agents like MMS are known mutagens.
- Mouse lymphoma L5178Y cells are a standard model for genotoxicity testing.
- Understanding differential mutagenic effects is crucial for risk assessment.
Purpose of the Study:
- To investigate the toxicity and mutagenicity of MMS in mouse lymphoma L5178Y cells.
- To compare the mutagenic efficiency of MMS with EMS for various resistance markers.
- To assess the induction of specific gene mutations by MMS.
Main Methods:
- Treatment of mouse lymphoma L5178Y cells with MMS.
- Dose-response analysis of cell toxicity and growth inhibition.
- Selection and quantification of thioguanine-, thymidine-, and ouabain-resistant variants.
- Comparison with EMS using a modified Luria-Delbrück fluctuation test.
Main Results:
- MMS exhibited dose-dependent toxicity and growth inhibition.
- MMS induced thioguanine- and thymidine-resistant variants, with a prolonged expression time.
- MMS was 10-fold more toxic than EMS but induced similar thymidine resistance at equal cell killing.
- MMS was less efficient than EMS for thioguanine resistance and did not induce ouabain resistance.
Conclusions:
- MMS is a potent mutagen with differential effects on specific gene mutations.
- The mutagenic profile of MMS differs significantly from EMS, particularly for ouabain resistance.
- These findings highlight the importance of selecting appropriate assays for evaluating mutagenic potential.
