• The hypersensitivity to alkylation damage is partly restored by depletion of Top1, illustrating that alkylating agents can trigger cytotoxic Top1-breaks. (whiterose.ac.uk)
  • 2010. Parp1 activation in mouse embryonic fibroblasts promotes Pol ß-dependent cellular hypersensitivity to alkylation damage. (setonhill.edu)
  • Base excision repair (BER) is the predominant DNA damage repair pathway for the processing of small base lesions, derived from oxidation and alkylation damages. (kegg.jp)
  • Importantly, alkylating agents induce DNA damage at different genomic sites, which subsequently leads to lethal and/or mutagenic DNA base lesions. (frontiersin.org)
  • He was the first to show that topoisomerases are trapped by DNA damage (by oxidative base lesions, base alkylation, DNA nicks) (Pourquier et al. (cancer.gov)
  • Nucleic acid damage by environmental and endogenous alkylation reagents creates lesions that are both mutagenic and cytotoxic, with the latter effect accounting for their widespread use in clinical cancer chemotherapy. (rcsb.org)
  • The Kumada coupling employs both a nucleophilic alkylation step subsequent to the oxidative addition of the aryl halide (L = Ligand , Ar = Aryl ). (wikipedia.org)
  • Direct DNA repair comprises several types of DNA repair enzymes that reversibly remove alkyl groups from damaged DNA bases through oxidative dealkylation processes. (frontiersin.org)
  • Apr 15, 2003 - Dr. Qingyi Wei, M.D. Anderson, Houston, Tx - DNA Repair Function, Polymorphisms and Cancer Risk in the General Population Mar 11, 2003 - Dr. Sankar Mitra, Univ of Texas, Galveston - Oxidative Damage Repair and Its Co-ordination in the Mammalian Genome. (bio.net)
  • SM can activate various cellular and molecular mechanisms related to oxidative stress (OS) and inflammatory responses throughout the reproductive system, which can cause decreased spermatogenesis and impaired sperm quality via damage to tissue function and structure. (nih.gov)
  • It is involved in damage reversal by oxidative demethylation of 1-methyladenine and 3-methylcytosine. (thermofisher.com)
  • It is well documented that oxidative stress induced by the environment and frontline chemotherapeutic drugs lead to DNA damage and apoptosis of photoreceptor cells [ 6 ]. (biomedcentral.com)
  • Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage[J]. Nature, 2002, 419(6903): 174-178. (shsmu.edu.cn)
  • HEKs exposure to the studied Me/MeO NCT (0-20 microg/cm2) resulted in a dose- and time-dependent reduction in cell viability, cell damage, activation of NF-kappaB, elevated ROS generation, release of inflammatory mediators, and increase in oxidative stress markers. (cdc.gov)
  • The E. coli alkB protein is part of the adaptive response mechanism of DNA alkylation damage repair. (thermofisher.com)
  • However, the exact downstream mechanism of alkylation-induced retinal degeneration needs further investigation. (biomedcentral.com)
  • Research of the structural function and regulation mechanism of ALKBH3 will help further understand the molecular mechanism in the DNA alkylation damage repair, and lay the foundation for the development of anti-tumor drugs targeting ALKBH3. (shsmu.edu.cn)
  • Damage Mechanism is a general term used to describe mechanical or chemical processes that result in equipment damage or material degradation. (inspectioneering.com)
  • As hydrogen-induced damage can occur in multiple forms, it's critical to identify the specific damage mechanism you're dealing with before undertaking measures to. (inspectioneering.com)
  • Base damage and topoisomerase I (Top1)-linked DNA breaks are abundant forms of endogenous DNA breakage, contributing to hereditary ataxia and underlying the cytotoxicity of a wide range of anti-cancer agents. (whiterose.ac.uk)
  • and endogenous pathways of DNA damage in the genesis of human cancer. (vanderbilt.edu)
  • Alkylating agents are reagents for effecting alkylation. (wikipedia.org)
  • Escherichia coli AlkB and the homologous human proteins ABH2 and ABH3 (refs 5, 7) promiscuously repair DNA and RNA bases damaged by S(N)2 alkylation reagents, which attach hydrocarbons to endocyclic ring nitrogen atoms (N1 of adenine and guanine and N3 of thymine and cytosine). (rcsb.org)
  • If DNA is alkylated during replication, then the replication fork can stall or collapse, and many repair mechanisms can be utilized to tolerate, bypass, or repair the damaged DNA. (nih.gov)
  • The extremely low 5-year overall survival of patients is, in part, due to pancreatic cancer cells having several mechanisms of resistance to different chemotherapeutic treatments, one of which is their capacity to efficiently repair alkylating agent-induced DNA damage. (frontiersin.org)
  • The key mechanisms include DNA alkylation, production of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide (NAD) depletion. (nih.gov)
  • DNA alkylation and/or inhibition of glutathione-scavenging pathways are 2 postulated mechanisms of action. (medscape.com)
  • Several possible mechanisms were considered for the induction of human leukemia, such as clastogenic damage to circulatory stem cells. (who.int)
  • For example, most methyl amines are prepared by alkylation of ammonia with methanol. (wikipedia.org)
  • In particular, certain types of ALKBH enzymes are dioxygenases that directly reverse DNA methylation damage via transfer of a methyl group from the DNA adduct onto α-ketoglutarate and release of metabolic products including succinate and formaldehyde. (frontiersin.org)
  • Following treatment with the alkylating agent methyl methane sulfonate (MMS), the C3 mRNA and protein level was measured, DNA damage and photoreceptor cell death were assessed in both wild-type (WT) C57BL/6J and C3 knockout (KO) mice. (biomedcentral.com)
  • ALKBH3 specifically recognizes N 1 -methyl adenine and N 3 -methyl cytosine on single-stranded DNA or RNA, and catalyzes their methyl group removal for alkylation damage repair. (shsmu.edu.cn)
  • Human nucleic acid alkylation damage repair enzyme ALKBH3 (alpha-ketoglutarate-dependent dioxygenase homolog 3) belongs to Fe 2+ /α-Ketoglutarate (α-KG)-dependent AlkB dioxygenase family, and shares a highly conserved catalytic domain through the entire family. (shsmu.edu.cn)
  • Function of human nucleic acid alkylation damage repair enzyme ALKBH3 in cancer progression and oncotherapy[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(5): 684-689. (shsmu.edu.cn)
  • DNA is susceptible to alkylation damage, particularly at nucleophilic sites located on purine and pyrimidine nucleobases. (hhs.gov)
  • We found that disruption of the yeast Shu complex leads to cellular death specifically upon exposure to alkylation induced DNA damage. (nih.gov)
  • In cancer treatment, targeting the cellular DNA or its nucleotide precursors has been a viable method for inhibiting the synthesis of new genetic material or causing irreparable damage to the DNA itself. (aacrjournals.org)
  • For upgrading of petroleum, alkylation produces a premium blending stock for gasoline. (wikipedia.org)
  • Currently, 46 of the 155 petroleum refineries in the U.S. have hydrofluoric alkylation units. (southphillyreview.com)
  • Hydrofluoric Acid (HF) Alkylation Units, often referred to as HF Alky units, are process units used in petroleum refining to convert isobutane and alkenes (primarily propylene or butylene) into. (inspectioneering.com)
  • Failure to repair DNA alkylation damage may lead to either or both mutagenesis or cytotoxicity. (hhs.gov)
  • However, whether C3 plays a critical role in alkylation-induced retinal degeneration is unclear. (biomedcentral.com)
  • N-, P-, and S-alkylation are important processes for the formation of carbon-nitrogen, carbon-phosphorus, and carbon-sulfur bonds, Amines are readily alkylated. (wikipedia.org)
  • Metal/metal oxide (Me/MeO) NP possess unique properties which can be useful in different applications including catalytic processes such as decomposition, reactions of dehydrogenation, oxidation, alkylation, C-C coupling, among others. (cdc.gov)
  • In parallel, Dr. Pommier has profoundly contributed to the elucidation of the repair pathways for topoisomerase-=induced DNA damage (Pommier et al. (cancer.gov)
  • Some symptoms of hydrofluoric exposure include irritation of the eyes, skin, nose and throat, eye and skin burns, rhinitis, bronchitis, fluid buildup in the lungs and bone damage. (southphillyreview.com)
  • Cracking is the the physical response in a material or piece of equipment to excessive exposure to damaging conditions. (inspectioneering.com)
  • The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. (bvsalud.org)
  • Hydrogen is a common culprit of equipment damage in the process industries. (inspectioneering.com)
  • To clarify why the men fell into the lake, a chemical analysis for hydrogen sulfide was carried out using the extractive alkylation technique combined with gas chromatography/mass spectrometry. (who.int)
  • This produces general toxic effects, such as myelosuppression, alopecia, damage to gastrointestinal epithelium, sterility and severe nausea and vomiting. (savedelicious.com)
  • In particular, the loss of ALKBH6 in human pancreatic cancer cells increases alkylating agent-induced DNA damage and significantly decreases cell survival. (frontiersin.org)
  • Here, we report that depletion of Tyrosyl DNA phosphodiesterase 1 (TDP1) sensitizes human cells to alkylation damage and the additional depletion of apurinic/apyrimidinic endonuclease I (APE1) confers hypersensitivity above that observed for TDP1 or APE1 depletion alone. (whiterose.ac.uk)
  • DNA damage responses in human induced pluripotent stem cells and embryonic stem cells. (setonhill.edu)
  • Workouts to try in the group who were also experienced weight lifters who had never include depression, hypertension, nervousness, acne, and even liver damage. (publicequalsonline.com)
  • The one most people know about is liver damage because of the so-called 17-alpha-alkylation. (muscle-gear.net)
  • Liver damage is the most infamous, but not the only downside of oral steroids. (muscle-gear.net)
  • Inhalation damages the respiratory tract epithelium and may cause death. (cdc.gov)
  • 7. Project Summary Misrepair of DNA damage is a hallmark of cancer. (nih.gov)
  • Here, we tested whether ALKBH6 plays a significant role in preventing alkylating DNA damage and decreasing genomic instability in pancreatic cancer cells. (frontiersin.org)
  • Finally, we demonstrate that cancer cells in which TDP1 is inherently deficient are hypersensitive to alkylation damage and that TDP1 depletion sensitizes glioblastoma-resistant cancer cells to the alkylating agent temozolomide. (whiterose.ac.uk)
  • What's more, among the genes that were most affected by the alkylation patterns were those that previous research has shown are among the most common drivers of colorectal cancer when they mutate. (ahram.org.eg)
  • Moderation urged - In this case, the suspicious mutation signature has a lot to answer for: patients whose tumors had the highest levels of alkylation damage had a 47 percent greater risk of colorectal cancer-specific death, compared to patients with lower levels of damage. (ahram.org.eg)
  • Alkylating agents, which are used as frontline chemotherapeutic drugs for cancer treatment, lead to extensive DNA damage in the body, which might cause retinal degeneration [ 4 ]. (biomedcentral.com)
  • Nov 12, 2002 - Dr. Rob Sobol, Univ of Pittsburgh - DNA Base Damage and Repair Intermediates: Out of the Pan and into the Fire [Note: The posting of this talk will be delayed at the request of the speaker. (bio.net)
  • Industry often relies on green chemistry methods involving alkylation of amines with alcohols, the byproduct being water. (wikipedia.org)
  • Although inhibition of PARP activity does not sensitize TDP1-deficient cells to Top1 poisons, it confers increased sensitivity to alkylation damage, highlighting partially overlapping roles for PARP and TDP1 in response to genotoxic challenge. (whiterose.ac.uk)
  • Our laboratory has focused on DNA damage by aldehydes produced endogenously in mammalian cells as a result of lipid peroxidation. (vanderbilt.edu)
  • A previous study also reported that retinal photoreceptor cells express P2X purinoceptor 7 (P2X7R) and that the P2X7 antagonist brilliant blue G (BBG), an approved adjuvant used in ocular surgery, prevents photoreceptor cell damage [ 7 ]. (biomedcentral.com)
  • Quantification of DNA breaks and clonogenic survival assays confirm a role for TDP1 in response to base damage, independently of APE1. (whiterose.ac.uk)
  • Here, we found that activation of C3 caused extensive DNA damage and that MMS treatment led to photoreceptor cell apoptosis. (biomedcentral.com)
  • In many cases the antiproloferation action is caused by damage to DNA, which initiates apoptosis and cell death [4]. (savedelicious.com)
  • Reactive and transient QMs and related electrophiles are formed during the metabolic activation of cytotoxic and genotoxic agents and may lead to DNA alkylation. (aacrjournals.org)
  • However, these sites are not equivalent, and alkylation of some sites may be more detrimental to DNA structure, integrity, and to the health of the cell than others. (hhs.gov)
  • Alkylation is a chemical reaction that entails transfer of an alkyl group. (wikipedia.org)
  • The Chemical Safety and Hazard Investigation Board said a corroded pipe elbow ruptured, releasing process fluid into the refinery's hydrofluoric acid alkylation unit. (southphillyreview.com)
  • There is a quantitative relationship between SCE and point-mutational damage of a base-substitutional nature although the relationship is different for each chemical investigated. (soton.ac.uk)
  • The largest example of this takes place in the alkylation units of petrochemical plants, which convert low-molecular-weight alkenes into high octane gasoline components. (wikipedia.org)
  • In general, DNA damage, cell death and defects in the cell membrane are frequently observed in SM-exposed individuals. (nih.gov)
  • Recipient of a supplemental grant to study the pluripotent stem cell response to DNA damage in response to the American Recovery and Reinvestment Act (ARRA) of 2009. (setonhill.edu)
  • In summary, our study found that C3 KO promotes photoreceptor cell survival and activates the Nrf2 signaling pathway in the context of alkylation-induced retinal degeneration. (biomedcentral.com)
  • Sedgwick B. Repairing DNA-methylation damage[J]. Nat Rev Mol Cell Biol, 2004, 5(2): 148-157. (shsmu.edu.cn)
  • Alkylation damage is caused by a myriad of industrial and consumer-based sources and is pervasive in our environment. (nih.gov)
  • The CSB also found that there were no remotely operated emergency isolation valves installed in the HF alkylation unit to isolate nearby hydrocarbon sources that could then flow through the failed elbow. (southphillyreview.com)
  • The analysis revealed a distinct mutational signature -- a pattern that had never before been identified but was indicative of a type of DNA damage called 'alkylation. (ahram.org.eg)
  • DNA methyltransferase ( MGMT , promotor-enhancer, can result in different dose-response relationships for 1099C/T). We also measured DNA damage (strand different groups of individuals. (cdc.gov)
  • The vapor also acts quickly, with pain on contact, followed by edema of the conjunctiva and eyelids, and iritis and corneal damage with high doses. (cdc.gov)