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Mutation Research Jan 1977
Topics: Animals; Female; Gene Frequency; Genes, Dominant; Genes, Lethal; Infertility, Male; Male; Mesylates; Methyl Methanesulfonate; Mice; Mutation; Pregnancy
PubMed: 191746
DOI: 10.1016/s0027-5107(77)80017-1 -
Mutation Research 2022Royal jelly (RJ) is a creamy white-yellow liquid that is secreted by the mandibular and hypopharyngeal glands of bees to nourish the larvae. RJ has gained increasing...
Royal jelly (RJ) is a creamy white-yellow liquid that is secreted by the mandibular and hypopharyngeal glands of bees to nourish the larvae. RJ has gained increasing interest in recent years owing to its antioxidant potential. However, little is known about adequate RJ dosing and its effects on genetic material. Thus, the aim of this study was to evaluate the in vivo effects of RJ on genotoxicity and mutagenicity induced by the alkylating agent methyl methanesulfonate (MMS). In this study, 3-month-old Swiss albino male mice (N = 66) were divided into 11 groups for experimentation. Experiments were performed by administering lyophilized RJ (150 mg/kg, 300 mg/kg, and 1000 mg/kg) or water via gavage as pre- and posttreatment processes with the alkylating agent MMS. After treatment, blood samples were collected from the mice via an incision at the end of the tail to conduct comet assays at times of 24 h and 48 h posttreatment. The mice were then euthanized to remove the bone marrow for a micronucleus test. Overall, regardless of dose, RJ did not exhibit genotoxic, mutagenic activity and the administration of high doses, mainly in the form of posttreatment, presented antigenotoxic and antimutagenic actions. Further, a dose-response correlation was observed in the RJ posttreatment groups. These results demonstrate that RJ administration was effective in reversing the damage caused by the alkylating agent MMS.
Topics: Mice; Bees; Animals; Alkylating Agents; DNA Damage; Fatty Acids; Comet Assay; Methyl Methanesulfonate; Mutagens
PubMed: 36007462
DOI: 10.1016/j.mrfmmm.2022.111796 -
Mutation Research Oct 1982We have used the method of combined bromodeoxyuridine density label and radioactive label to measure the size of the repair patches appearing in the DNA of KB cells...
We have used the method of combined bromodeoxyuridine density label and radioactive label to measure the size of the repair patches appearing in the DNA of KB cells following treatment with UV-light or MMS. The repair patch size distribution was found to be the same for both agents, corresponding to the insertion of 34-40 nucleotides. These results, confirm recent results obtained by the bromodeoxyuridine-photolysis technique, that simple alkylating agents induce 'long patch' repair in human cells.
Topics: Bromodeoxyuridine; Cell Line; DNA Repair; Humans; Methyl Methanesulfonate; Molecular Weight; Ultraviolet Rays
PubMed: 7133035
DOI: 10.1016/0165-7992(82)90042-2 -
Chemico-biological Interactions 1983DNA strand breakage and repair following methyl methanesulfonate (MMS) treatment of primary cell cultures from 14-day fetal Sprague-Dawley rat brain and liver and 12-day...
DNA strand breakage and repair following methyl methanesulfonate (MMS) treatment of primary cell cultures from 14-day fetal Sprague-Dawley rat brain and liver and 12-day fetal C57BL/6 mouse brain and liver, were studied using alkaline sucrose density gradient analysis. Cells were incubated with MMS (7 mM or 14 mM) for 20 min and harvested for alkaline sucrose gradients 40 min or 24 h later. The extent of initial damage in fetal rat and fetal mouse cells was comparable. Fetal mouse brain and liver and rat liver showed nearly complete repair 24 h after treatment. However, fetal rat brain cells showed comparatively little repair after 24 h. The possible significance of a repair deficit in cultured rat fetal brain cells and the striking neurogenic organotropism of transplacentally administered direct-acting alkylating agents in the rat is discussed.
Topics: Animals; Brain Chemistry; Cells, Cultured; Centrifugation, Density Gradient; DNA; DNA Repair; Liver; Methyl Methanesulfonate; Mice; Mice, Inbred C57BL; Molecular Weight; Rats; Rats, Inbred Strains
PubMed: 6850927
DOI: 10.1016/0009-2797(83)90130-8 -
Chemical Research in Toxicology Dec 2006The chemical methylating agents methylmethane sulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) have been used for decades as classical DNA damaging... (Review)
Review
The chemical methylating agents methylmethane sulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) have been used for decades as classical DNA damaging agents. These agents have been utilized to uncover and explore pathways of DNA repair, DNA damage response, and mutagenesis. MMS and MNNG modify DNA by adding methyl groups to a number of nucleophilic sites on the DNA bases, although MNNG produces a greater percentage of O-methyl adducts. There has been substantial progress elucidating direct reversal proteins that remove methyl groups and base excision repair (BER), which removes and replaces methylated bases. Direct reversal proteins and BER, thus, counteract the toxic, mutagenic, and clastogenic effects of methylating agents. Despite recent progress, the complexity of DNA damage responses to methylating agents is still being discovered. In particular, there is growing understanding of pathways such as homologous recombination, lesion bypass, and mismatch repair that react when the response of direct reversal proteins and BER is insufficient. Furthermore, the importance of proper balance within the steps in BER has been uncovered with the knowledge that DNA structural intermediates during BER are deleterious. A number of issues complicate the elucidation of the downstream responses when direct reversal is insufficient or BER is imbalanced. These include inter-species differences, cell-type-specific differences within mammals and between cancer cell lines, and the type of methyl damage or BER intermediate encountered. MMS also carries a misleading reputation of being a radiomimetic, that is, capable of directly producing strand breaks. This review focuses on the DNA methyl damage caused by MMS and MNNG for each site of potential methylation to summarize what is known about the repair of such damage and the downstream responses and consequences if the damage is not repaired.
Topics: Animals; DNA Breaks; DNA Methylation; DNA Repair; Humans; Methyl Methanesulfonate; Methylnitronitrosoguanidine
PubMed: 17173371
DOI: 10.1021/tx060164e -
International Journal of Radiation... 2023Many articles describe the effects of extremely low-frequency magnetic fields (MFs) on DNA damage induction. However, the mechanism of MF interaction with living matter...
PURPOSE
Many articles describe the effects of extremely low-frequency magnetic fields (MFs) on DNA damage induction. However, the mechanism of MF interaction with living matter is not yet known with certainty. Some works suggest that MF could induce an increase in the efficacy of reactive oxygen species (ROS) production. This work investigates whether pulsed MF exposure produces alterations in genomic DNA damage induced by co-exposure to DNA damaging agents (bleomycin and methyl methanesulfonate (MMS)).
MATERIALS AND METHODS
Genomic DNA, prepared from cultures, was exposed to pulsed MF (1.5 mT peak, 25 Hz) and MMS (0-1%) (15-60 min), and to MF and bleomycin (0-0.6 IU/mL) (24-72 h). The damage induced to DNA was evaluated by electrophoresis and image analysis.
RESULTS
Pulsed MF induced an increment in the level of DNA damage produced by MMS and bleomycin in all groups at the exposure conditions assayed.
CONCLUSIONS
Pulsed MF could modulate the cytotoxic action of MMS and bleomycin. The observed effect could be the result of a multifactorial process influenced by the type of agent that damages DNA, the dose, and the duration of the exposure to the pulsed MF.
Topics: Saccharomyces cerevisiae; Magnetic Fields; DNA Damage; Methyl Methanesulfonate; DNA; Genomics
PubMed: 36069754
DOI: 10.1080/09553002.2022.2121873 -
ELife Mar 2022DNA base damage arises frequently in living cells and needs to be removed by base excision repair (BER) to prevent mutagenesis and genome instability. Both the formation...
DNA base damage arises frequently in living cells and needs to be removed by base excision repair (BER) to prevent mutagenesis and genome instability. Both the formation and repair of base damage occur in chromatin and are conceivably affected by DNA-binding proteins such as transcription factors (TFs). However, to what extent TF binding affects base damage distribution and BER in cells is unclear. Here, we used a genome-wide damage mapping method, -methylpurine-sequencing (NMP-seq), and characterized alkylation damage distribution and BER at TF binding sites in yeast cells treated with the alkylating agent methyl methanesulfonate (MMS). Our data show that alkylation damage formation was mainly suppressed at the binding sites of yeast TFs ARS binding factor 1 (Abf1) and rDNA enhancer binding protein 1 (Reb1), but individual hotspots with elevated damage levels were also found. Additionally, Abf1 and Reb1 binding strongly inhibits BER in vivo and in vitro, causing slow repair both within the core motif and its adjacent DNA. Repair of ultraviolet (UV) damage by nucleotide excision repair (NER) was also inhibited by TF binding. Interestingly, TF binding inhibits a larger DNA region for NER relative to BER. The observed effects are caused by the TF-DNA interaction, because damage formation and BER can be restored by depletion of Abf1 or Reb1 protein from the nucleus. Thus, our data reveal that TF binding significantly modulates alkylation base damage formation and inhibits repair by the BER pathway. The interplay between base damage formation and BER may play an important role in affecting mutation frequency in gene regulatory regions.
Topics: DNA; DNA Damage; DNA Repair; Methyl Methanesulfonate; Transcription Factors
PubMed: 35289750
DOI: 10.7554/eLife.73943 -
Journal of Natural Products Dec 2012Glucoputranjivin (1) and isopropyl isothiocyanate (2) were isolated from an aqueous dry extract of Sisymbrium officinale and were identified by spectroscopic analysis....
Glucoputranjivin (1) and isopropyl isothiocyanate (2) were isolated from an aqueous dry extract of Sisymbrium officinale and were identified by spectroscopic analysis. The antimutagenic activity of these compounds was evaluated in a bacterial reverse mutation assay using E. coli WP2, WP2uvrA, and WP2uvrA/pKM101 strains, in comparison with the extract. In the absence of the exogenous metabolic activation system S9, the thio compounds exerted antimutagenic activity against the direct-acting mutagen methyl methanesulfonate, in all strains. In the presence of S9, both thio compounds were active against the indirect mutagens 2-aminoanthracene, in WP2uvrA, and 2-aminofluorene, in WP2. The antimutagenicity seems to be due to specific mechanisms, such as the induction of the adaptive response or the excision repair system. Conversely, the inhibition of the CYP450-mediated activation of mutagens was not supported by the present results. An antimutagenic effect was also observed for the S. officinale aqueous extract against the arylamines 2AA and 2AF, but not against MMS. These results suggest that both thio compounds are involved in the antimutagenicity of S. officinale. The antimutagenicity of glucosinolate 1 is reported for the first time.
Topics: Antimutagenic Agents; Brassicaceae; Glucosinolates; Isothiocyanates; Methyl Methanesulfonate; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Tryptophan
PubMed: 23193942
DOI: 10.1021/np300244q -
Medical Science Monitor : International... Jun 2002The alkylation of nucleic acids is primarily responsible for chemical carcinogenesis. Even during disease treatment, several alkylating drugs interact with nucleic acids...
BACKGROUND
The alkylation of nucleic acids is primarily responsible for chemical carcinogenesis. Even during disease treatment, several alkylating drugs interact with nucleic acids and cause severe toxic effects. Thus good chemoprotectants are necessary. For our study we chose a simple model organism, bacteriophage T4 (a nucleoprotenic particle), and alkylating agent methyl methanesulfonate (MMS) to study its lethal effects. Sodium thiosulfate (STS), used as a chemoprotectant, has been tested against alkylating drugs.
MATERIAL/METHODS
Bacteriophage T4D(o) were exposed to different molarities of MMS for several pre-termination incubations. Alkylation reactions were stopped with different concentrations of STS at given pre-termination incubation periods and further incubated up to 24 hours. The viability (survival frequency) of phage T4 was studied at various post-termination intervals by plaque count assay.
RESULTS
Our results show that the survival frequency is strongly influenced by MMS dosage and exposure time. However, the antidotal effect of STS on MMS-induced lethality directly corresponds to STS dosage. Survival frequencies with 1% quench solution were lower than with 5% quench solution at all molarities of MMS and at different pre- and post-termination periods.
CONCLUSIONS
Our studies confirmed the role of STS in the cytoprotection of bacteriophage T4. In the presence of 1% STS, a moderate inhibition in cytotoxicity was observed, while 5% STS exhibited a significant inhibition against the cytotoxic activity of MMS, presumably due to a rapid covalent binding of the methyl group (carbocation - an electrophile) of MMS with the nucleophilic sulfur atom of STS.
Topics: Bacteriophage T4; Methyl Methanesulfonate; Mutagenesis; Thiosulfates
PubMed: 12070426
DOI: No ID Found -
Mutation Research Jan 1989In contrast to earlier reports (Mohn et al., 1980; Glickman, 1982), we show that E. coli dam- cells are able to mutate following MMS treatment. Since the mutagenicity of...
In contrast to earlier reports (Mohn et al., 1980; Glickman, 1982), we show that E. coli dam- cells are able to mutate following MMS treatment. Since the mutagenicity of MMS has been regarded as largely dependent on induction of the SOS functions, E. coli strains bearing the recA::lacZ or umuC::lacZ fusions were used to determine the ability of MMS to induce the SOS functions in the various dam+ and dam- strains. The mutagenicity of MMS was also tested in several of these strains. The results show that (i) there is no direct correlation between SOS-inducing ability and mutagenicity potency of MMS; and (ii) most of the premutagenic lesions induced by MMS are removed from DNA of dam+ or dam- cells by the mismatch repair system. The role of strand breaks in repair of mismatches induced by alkylating agents is discussed.
Topics: DNA Repair; DNA, Bacterial; Escherichia coli; Genes, Bacterial; Methyl Methanesulfonate; Mutagenicity Tests; Mutation; SOS Response, Genetics
PubMed: 2642600
DOI: 10.1016/0027-5107(89)90039-0