Ethyl methanesulfonate: Difference between revisions
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== Repair of mutagenic lesion == |
== Repair of mutagenic lesion == |
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''O''<sup>6</sup>-ethylguanine can be repaired ''in vivo'' in a stoichiometric fashion by reacting with the active site cysteine of the [[O-6-methylguanine-DNA_methyltransferase]] repair protein.<ref name="Pegg 2000 pp. 83–100">{{cite journal | last=Pegg | first=Anthony E | title=Repair of O6-alkylguanine by alkyltransferases | journal=Mutation Research/Reviews in Mutation Research | publisher=Elsevier BV | volume=462 | issue=2-3 | year=2000 | issn=1383-5742 | doi=10.1016/s1383-5742(00)00017-x | pages=83–100}}</ref> The ''in vivo'' half-life of ''O''<sup>6</sup>-ethylguanine was reported to be about 9 days in mouse brain, while it was about 1 day in mouse liver.<ref name="Goth Rajewsky pp. 639–643">{{cite journal | last=Goth | first=R. | last2=Rajewsky | first2=M. F. | title=Persistence of O6-Ethylguanine in Rat-Brain DNA: Correlation with Nervous System-Specific Carcinogenesis by Ethylnitrosourea | journal=Proceedings of the National Academy of Sciences | publisher=Proceedings of the National Academy of Sciences | volume=71 | issue=3 | date=1974-03-01 | issn=0027-8424 | doi=10.1073/pnas.71.3.639 | pages=639–643}}</ref> |
''O''<sup>6</sup>-ethylguanine can be repaired ''in vivo'' in a stoichiometric fashion by reacting with the active site cysteine of the [[O-6-methylguanine-DNA_methyltransferase]] repair protein.<ref name="Pegg 2000 pp. 83–100">{{cite journal | last=Pegg | first=Anthony E | title=Repair of O6-alkylguanine by alkyltransferases | journal=Mutation Research/Reviews in Mutation Research | publisher=Elsevier BV | volume=462 | issue=2-3 | year=2000 | issn=1383-5742 | doi=10.1016/s1383-5742(00)00017-x | pages=83–100}}</ref> The ''in vivo'' half-life of ''O''<sup>6</sup>-ethylguanine was reported to be about 9 days in mouse brain, while it was about 1 day in mouse liver.<ref name="Goth Rajewsky pp. 639–643">{{cite journal | last=Goth | first=R. | last2=Rajewsky | first2=M. F. | title=Persistence of O6-Ethylguanine in Rat-Brain DNA: Correlation with Nervous System-Specific Carcinogenesis by Ethylnitrosourea | journal=Proceedings of the National Academy of Sciences | publisher=Proceedings of the National Academy of Sciences | volume=71 | issue=3 | date=1974-03-01 | issn=0027-8424 | doi=10.1073/pnas.71.3.639 | pages=639–643}}</ref> |
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== Stability == |
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Generally speaking EMS is unstable in water, and undergoes hydrolysis to ethanol and methanesulfonic acid, however at neutral to acidic pH at room temperature, it's half-life is fairly long at over 1 day.<ref name="FROESE-GERTZEN KONZAK FOSTER NILAN 1963 pp. 447–448">{{cite journal | last=FROESE-GERTZEN | first=EDITH E. | last2=KONZAK | first2=C. F. | last3=FOSTER | first3=R. | last4=NILAN | first4=R. A. | title=Correlation between Some Chemical and Biological Reactions of Ethyl Methanesulphonate | journal=Nature | publisher=Springer Science and Business Media LLC | volume=198 | issue=4879 | year=1963 | issn=0028-0836 | doi=10.1038/198447a0 | pages=447–448}}</ref><ref name="Afza2003">{{cite book | last=Kodym | first=Andrea | last2=Afza | first2=Rownak | chapter=Chapter 12 Physical and Chemical Mutagenesis| title=Plant functional genomics | publisher=Humana Press | publication-place=Totowa, N.J | year=2003 | isbn=978-1-58829-145-5 | oclc=51445955 | page=189-203}}</ref> |
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==See also== |
==See also== |
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Revision as of 00:36, 11 August 2021
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| Names | |
|---|---|
| Preferred IUPAC name
Ethyl methanesulfonate | |
| Other names
Ethyl mesylate
Ethyl methanesulphonate | |
| Identifiers | |
3D model (JSmol)
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| Abbreviations | EMS |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.000.488 |
| KEGG | |
PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| CH3SO3C2H5 | |
| Molar mass | 124.16 g/mol |
| Appearance | Clear colorless liquid |
| Density | 1.1452 g/cm3 (22 °C) |
| Melting point | < 25 °C |
| Boiling point | 85–86 °C (185–187 °F; 358–359 K) /10 mmHg(lit) |
| Vapor pressure | 0.044 kPa @ 25˚C[2] |
| Hazards | |
| NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Ethyl methanesulfonate (EMS) is a mutagenic, teratogenic, and carcinogenic organic compound with formula C3H8SO3. It produces random mutations in genetic material by nucleotide substitution; particularly through G:C to A:T transitions induced by guanine alkylation.[3] EMS typically produces only point mutations. Due to its potency and well understood mutational spectrum, EMS is the most commonly used chemical mutagen in experimental genetics.[4] Mutations induced by EMS exposure can then be studied in genetic screens or other assays.
Use in biological research
EMS can induce mutations at a rate of 5x10−4 to 5x10−2 per gene without substantial killing. A 5x10−4 per gene mutation rate observed in a typical EMS mutagenesis experiment of the model organism C. elegans, corresponds to a raw mutation rate of ~7x10−6 mutations per G/C base pair, or about 250 mutations within an originally mutagenized gamete (containing a ~100 Mbp, 36% GC haploid genome).[5] Such a mutagenized gamete would have about 9 different loss-of-function mutations in genes, with 1 to 2 of these mutations being within essential genes and therefore lethal. However, since it is unlikely the same essential gene is mutated in independent gametes, and if loss of the essential gene did not kill the gamete itself, downstream gamete fusion often allows for survival of the resulting zygote and organism, as the now heterozygous non-functional mutated allele may be rescued by the still wildtype allele provided by the other gamete.[5]
Mechanism of mutagenesis
The ethyl group of EMS reacts with guanine in DNA, forming the abnormal base O6-ethylguanine. During DNA replication, DNA polymerases that catalyze the process frequently place thymine, instead of cytosine, opposite O6-ethylguanine. Following subsequent rounds of replication, the original G:C base pair can become an A:T pair (a transition mutation). This changes the genetic information, is often harmful to cells, and can result in disease. RNA polymerase can also place uridine (RNA analog of thymine) opposite an O6-ethylguanine lesion.[6]
Repair of mutagenic lesion
O6-ethylguanine can be repaired in vivo in a stoichiometric fashion by reacting with the active site cysteine of the O-6-methylguanine-DNA_methyltransferase repair protein.[7] The in vivo half-life of O6-ethylguanine was reported to be about 9 days in mouse brain, while it was about 1 day in mouse liver.[8]
Stability
Generally speaking EMS is unstable in water, and undergoes hydrolysis to ethanol and methanesulfonic acid, however at neutral to acidic pH at room temperature, it's half-life is fairly long at over 1 day.[9][10]
See also
References
- ^ Merck Index, 11th Edition, 3782.
- ^ "Ethyl Methanesulfonate" (PDF). Report on Carcinogens, Fourteenth Edition. NIEHS. Retrieved 18 June 2021.
- ^ Sega, Gary A. (1984). "A review of the genetic effects of ethyl methanesulfonate". Mutation Research/Reviews in Genetic Toxicology. 134 (2–3). Elsevier BV: 113–142. doi:10.1016/0165-1110(84)90007-1. ISSN 0165-1110.
- ^ Kutscher, Lena M.; Shaham, Shai. "Forward and reverse mutagenesis in C. elegans". WormBook. Retrieved 18 June 2021.
- ^ a b Anderson, Philip (1995). "Chapter 2 Mutagenesis". Caenorhabditis elegans: Modern Biological Analysis of an Organism. Elsevier. pp. 31–58. doi:10.1016/s0091-679x(08)61382-5. ISBN 978-0-12-564149-4. ISSN 0091-679X.
- ^ Gerchman, Lois L.; Ludlum, David B. (1973). "The properties of in templates for RNA polymerase". Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis. 308 (2). Elsevier BV: 310–316. doi:10.1016/0005-2787(73)90160-3. ISSN 0005-2787.
- ^ Pegg, Anthony E (2000). "Repair of O6-alkylguanine by alkyltransferases". Mutation Research/Reviews in Mutation Research. 462 (2–3). Elsevier BV: 83–100. doi:10.1016/s1383-5742(00)00017-x. ISSN 1383-5742.
- ^ Goth, R.; Rajewsky, M. F. (1974-03-01). "Persistence of O6-Ethylguanine in Rat-Brain DNA: Correlation with Nervous System-Specific Carcinogenesis by Ethylnitrosourea". Proceedings of the National Academy of Sciences. 71 (3). Proceedings of the National Academy of Sciences: 639–643. doi:10.1073/pnas.71.3.639. ISSN 0027-8424.
- ^ FROESE-GERTZEN, EDITH E.; KONZAK, C. F.; FOSTER, R.; NILAN, R. A. (1963). "Correlation between Some Chemical and Biological Reactions of Ethyl Methanesulphonate". Nature. 198 (4879). Springer Science and Business Media LLC: 447–448. doi:10.1038/198447a0. ISSN 0028-0836.
- ^ Kodym, Andrea; Afza, Rownak (2003). "Chapter 12 Physical and Chemical Mutagenesis". Plant functional genomics. Totowa, N.J: Humana Press. p. 189-203. ISBN 978-1-58829-145-5. OCLC 51445955.