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IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Humans; Methyl Methanesulfonate; Mutagenicity Tests; Mutagens; Neoplasms, Experimental
PubMed: 10476376
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Carcinogenicity Tests; Carcinogens, Environmental; Humans; Methyl Methanesulfonate; Mice; Molecular Structure; Occupational Exposure; Rats
PubMed: 21860482
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2004
Topics: Animals; Antineoplastic Agents, Alkylating; Carcinogenicity Tests; Carcinogens; Female; Government Regulation; Guidelines as Topic; Humans; Male; Methyl Methanesulfonate; Mice; Models, Biological; Occupational Exposure; Rats; United States
PubMed: 21089907
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2002
Topics: Animals; Carcinogens; Environmental Exposure; Government Regulation; Humans; Methyl Methanesulfonate; United States
PubMed: 15326675
DOI: No ID Found -
Journal of Separation Science Sep 2017Methanesulfonic acid is routinely used in pharmaceuticals but can contain potentially genotoxic impurities such as methyl methanesulfonate and ethyl methanesulfonate....
Determination of methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid by derivatization followed by high-performance liquid chromatography with ultraviolet detection.
Methanesulfonic acid is routinely used in pharmaceuticals but can contain potentially genotoxic impurities such as methyl methanesulfonate and ethyl methanesulfonate. The aim of this study was to develop a simple high-performance liquid chromatography with ultraviolet detection method for determining methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid. Samples (250 mg) in water/acetonitrile (200 μL) were first combined with 10.0 mol/L sodium hydroxide solution (270 μL). Then they were mixed with 2.0 mg/mL N,N-diethyldithiocarbamate (500 μL), diluted to 5 mL with N,N-dimethylacetamide and allowed to react at 80°C for 1 h. The derivatives were analyzed using gradient high-performance liquid chromatography with ultraviolet detection (277 nm) and structurally elucidated by liquid chromatography with mass spectrometry. With acetonitrile/5 mmol/L ammonium acetate solution as the eluent and 1 mL/min as the flow rate on a C18 column, the derivatives were eluted at 10.6 and 14.8 min. Good linearity (correlation coefficients > 0.999) and low limits of quantitation (0.6 ppm) were obtained. The recoveries were in the range of 80-115% with relative standard deviation < 5.0%. Finally, the established method was successfully used for the determination of methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid.
Topics: Chromatography, High Pressure Liquid; Drug Contamination; Ethyl Methanesulfonate; Mesylates; Methyl Methanesulfonate
PubMed: 28675589
DOI: 10.1002/jssc.201700543 -
Chemical Research in Toxicology Dec 2020Allergic contact dermatitis (ACD) is a reaction of the immune system resulting from skin sensitization to an exogenous hazardous chemical and leading to the activation...
Allergic contact dermatitis (ACD) is a reaction of the immune system resulting from skin sensitization to an exogenous hazardous chemical and leading to the activation of antigen-specific T-lymphocytes. The adverse outcome pathway (AOP) for skin sensitization identified four key events (KEs) associated with the mechanisms of this pathology, the first one being the ability of skin chemical sensitizers to modify epidermal proteins to form antigenic structures that will further trigger the immune system. So far, these interactions have been studied in solution using model nucleophiles such as amino acids or peptides. As a part of our efforts to better understand chemistry taking place during the sensitization process, we have developed a method based on the use of high-resolution magic angle spinning (HRMAS) NMR to monitor in situ the reactions of C substituted chemical sensitizers with nucleophilic amino acids of epidermal proteins in reconstructed human epidermis. A quantitative approach, developed so far for liquid NMR applications, has not been developed to our knowledge in a context of a semisolid nonanisotropic environment like the epidermis. We now report a quantitative chemical reactivity mapping of methyl methanesulfonate (MMS), a sensitizing methylating agent, in reconstructed human epidermis by quantitative HRMAS (qHRMAS) NMR. First, the haptenation process appeared to be much faster in RHE than in solution with a maximum concentration of adducts reached between 4 and 8 h. Second, it was observed that the concentration of cysteine adducts did not significantly increase with the dose (2.07 nmol/mg at 0.4 M and 2.14 nmol/mg at 1 M) nor with the incubation time (maximum of 2.27 nmol/mg at 4 h) compared to other nucleophiles, indicating a fast reaction and a potential saturation of targets. Third, when increasing the exposure dose, we observed an increase of adducts up to 12.5 nmol/mg of RHE, excluding cysteine adducts, for 3112 μg/cm (1 M solution) of . This methodology applied to other skin sensitizers could allow for better understanding of the potential links between the amount of chemical modifications formed in the epidermis in relation to exposure and the sensitization potency.
Topics: Alkylation; Cells, Cultured; Dermatitis, Allergic Contact; Epidermis; Humans; Magnetic Resonance Spectroscopy; Methyl Methanesulfonate; Molecular Structure
PubMed: 33190492
DOI: 10.1021/acs.chemrestox.0c00362 -
Genetics Dec 1982MMS induces diverse rII mutations from a wild-type background in bacteriophage T4. About 56% are base pair substitutions, about 30% are frameshift mutations, and the...
MMS induces diverse rII mutations from a wild-type background in bacteriophage T4. About 56% are base pair substitutions, about 30% are frameshift mutations, and the remainder is a miscellaneous set of rapidly reverting or leaky mutants of unknown composition; but deletions were not detected. MMS-induced forward mutation is sharply reduced by the mutations px and y, which also reduce ultraviolet, photodynamic and gamma-ray mutagenesis and increase killing by all of these agents. Thus, many of the mutations arise via the T4 WXY system. The induction of G:C leads to A:T transitions was detected even in a px or y background using sensitive reversion tests, and the few forward rII mutations that were induced from this background also behaved like transition mutations. Thus, some MMS-induced mutations arise independently of the WXY system, perhaps as a result of the (rather weak) ability of MMS to alkylate the O6 position of guanine.
Topics: Genes, Lethal; Genes, Viral; Methyl Methanesulfonate; Mutation; T-Phages
PubMed: 7187361
DOI: 10.1093/genetics/102.4.639 -
Biotechnic & Histochemistry : Official... 2016Methylmethane sulfonate (MMS) is an alkylating agent that may react with DNA and damage it. We investigated histological changes and apoptosis caused by MMS and the...
Methylmethane sulfonate (MMS) is an alkylating agent that may react with DNA and damage it. We investigated histological changes and apoptosis caused by MMS and the effects of curcumin on MMS treated mouse kidneys. Twenty-four mice were divided into four equal groups: controls injected with saline, a group injected with 40 mg/kg MMS, a group injected with 40 mg/kg MMS and given 100 mg/kg curcumin by gavage, and a group given 100 mg/kg curcumin by gavage. MMS caused congestion and vacuole formation, and elevated the apoptotic index significantly, but had no other effect on kidney tissue. Curcumin improved the congestion and vacuole formation caused by MMS and decreased the apoptotic index. Curcumin administered with MMS appears to decrease the deleterious effects of MMS on the kidney.
Topics: Acute Kidney Injury; Animals; Curcumin; DNA; Kidney; Methyl Methanesulfonate; Mice
PubMed: 26529305
DOI: 10.3109/10520295.2015.1099737 -
Acta Biochimica Polonica 1998Methyl methanesulfonate (MMS) is an SN2 type alkylating agent which predominantly methylates nitrogen atoms in purines. Among the methylated bases 3meA and 3meG are... (Review)
Review
Methyl methanesulfonate (MMS) is an SN2 type alkylating agent which predominantly methylates nitrogen atoms in purines. Among the methylated bases 3meA and 3meG are highly mutagenic and toxic. The excision of these lesions leads to the formation of apurinic (AP) sites and subsequently to AT-->TA or GC-->TA transversions. The in vivo method based on phenotypic analysis of Arg+ revertants of Escherichia coli K12 and sensitivity to T4 nonsense mutants has been used to estimate the specificity of MMS induced mutations. In the E. coli arg-his-thr- (AB1157) strain MMS induces argE3(oc)-->Arg+ revertants of which 70-80% arise by supL suppressor formation as a result of AT-->TA transversions. The remaining 20-30% arise by supB and supE(oc) suppressor formation as a result of GC-->AT transitions. The level of AT-->TA transversions decreases during starvation. This is a consequence of action of the repair mechanism called mutation frequency decline. This system which is a transcription coupled variant of nucleotide excision repair was discovered in UV induced mutations. We describe the mutation frequency decline phenomenon for MMS mutagenesis. MMS is a very efficient inducer of the SOS response and a umuDC dependent mutagen. In MMS treated E. coli cells mutated in umuDC genes the class of AT-->TA transversions dramatically diminishes. A plasmid bearing UmuD(D')C proteins can supplement chromosomal deletion of umuDC operon: a plasmid harbouring umuD'C is more efficient in comparison to that harbouring umuDC. Moreover, plasmids isolated from MMS treated and transiently starved E. coli AB1157 cells harbouring umuD(D')C genes have shown the repair of AP sites by a system which involves the UmuD'C or at least UmuD' protein.
Topics: Animals; DNA Repair; Escherichia coli; Methyl Methanesulfonate; Mutagenesis; Mutagens; Mutation
PubMed: 9821881
DOI: No ID Found -
Environmental Science and Pollution... Nov 2023In this study, the toxicity induced by the alkylating agent methyl methanesulfonate (MMS) in Allium cepa L. was investigated. For this aim, bulbs were divided into 4...
In this study, the toxicity induced by the alkylating agent methyl methanesulfonate (MMS) in Allium cepa L. was investigated. For this aim, bulbs were divided into 4 groups as control and application (100, 500 and 4000 µM MMS) and germinated for 72 h at 22-24 °C. At the end of the germination period root tips were collected and made ready for analysis by applying traditional preparation methods. Germination, root elongation, weight, mitotic index (MI) values, micronucleus (MN) and chromosomal abnormality (CAs) numbers, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities and anatomical structures of bulbs were used as indicators to determine toxicity. Moreover the extent of DNA fragmentation induced by MMS was determined by comet assay. To confirm the DNA fragmentation induced by MMS, the DNA-MMS interaction was examined with molecular docking. Correlation and principal component analyses (PCA) were performed to examine the relationship between all parameters and understand the underlying structure and relationships among these parameters. In the present study, a deep neural network (DNN) with two hidden layers implemented in Matlab has been developed for the comparison of the estimated data with the real data. The effect of MDA levels, SOD and CAT activities at 4 different endpoints resulting from administration of various concentrations of MMS, including MN, MI, CAs and DNA damage, was attempted to be estimated by DNN model. It is assumed that the predicted results are in close agreement with the actual data. The effectiveness of the model was evaluated using 4 different metrics, MAE, MAPE, RMSE and R2, which together show that the model performs commendably. As a result, the highest germination, root elongation, weight gain and MI were measured in the control group. MMS application caused a decrease in all physiological parameters and an increase in cytogenetic (except MI) and biochemical parameters. MMS application caused an increase in antioxidant enzyme levels (SOD and CAT) up to a concentration of 500 µM and a decrease at 4000 µM. MMS application induced different types of CAs and anatomical damages in root meristem cells. The results of the comet assay showed that the severity of DNA fragmentation increased with increasing MMS concentration. Molecular docking analysis showed a strong DNA-MMS interaction. The results of correlation and PCA revealed significant positive and negative interactions between the studied parameters and confirmed the interactions of these parameters with MMS. It has been shown that the DNN model developed in this study is a valuable resource for predicting genotoxicity due to oxidative stress and lipid peroxidation. In addition, this model has the potential to help evaluate the genotoxicity status of various chemical compounds. At the end of the study, it was concluded that MMS strongly supports a versatile toxicity in plant cells and the selected parameters are suitable indicators for determining this toxicity.
Topics: Methyl Methanesulfonate; Molecular Docking Simulation; Antioxidants; Plant Roots; Meristem; Superoxide Dismutase; Chromosome Aberrations; Onions; DNA; DNA Damage
PubMed: 37874518
DOI: 10.1007/s11356-023-30465-0