DNA repair mechanisms in response to genotoxicity of warfare agent sulfur mustard

Published on Feb 2, 2018in Environmental Toxicology and Pharmacology4.86
路 DOI :10.1016/J.ETAP.2018.01.012
Yunes Panahi39
Estimated H-index: 39
(BMSU: Baqiyatallah University of Medical Sciences),
Amir Fattahi13
Estimated H-index: 13
(Tabriz University of Medical Sciences)
+ 4 AuthorsTohid Ghasemnejad7
Estimated H-index: 7
(Tabriz University of Medical Sciences)
Sources
Abstract
Abstract Sulfur mustard (SM) is an alkylating agent that causes severe damages to the skin, eyes, and the respiratory system. DNA alkylation is one of the most critical lesions that could lead to monoadducts and cross-links, as well as DNA strand breaks. In response to these adducts, cells initiate a series of reactions to recruit specific DNA repair pathways. The main DNA repair pathways in human cells, which could be involved in the DNA SM-induced DNA damages, are base excision repair (BER), nucleotide excision repair (NER), homologous recombination (HR) and non-homologous end joining (NHEJ). There is, thus, a need for a short review to clarify which damage caused by SM is repaired by which repair pathway. Increasing our knowledge about different DNA repair mechanisms following SM exposure would lay the first step for developing new therapeutic agents to treat people exposed to SM. In this review, we describe the major DNA repair pathways, according to the DNA adducts that can be caused by SM.
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Many effective agents used in cancer chemotherapy cause DNA interstrand crosslinks (ICLs), which covalently link both strands of the double helix together resulting in cytotoxicity. ICLs are thought to be processed by proteins from a variety of DNA repair pathways; however, a clear understanding of ICL recognition and repair processing in human cells is lacking. Previously, we found that the high mobility group box 1 (HMGB1) protein bound to triplex-directed psoralen ICLs (TFO-ICLs) in vitro, co...
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Sulphur mustard (SM) is known as an efficient vesicating agent as well as a carcinogenic chemical. This warfare agent remains a threat for both civilians and militaries. DNA alkylation is one of the critical molecular pathways at the origin of the symptoms associated with SM exposure. SM forms monoadducts with guanine and adenine as well as a biadduct between two guanine bases. The aim of the present work is to determine the relative yields of these three lesions in DNA samples after SM exposure...
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Iranian soldiers were attacked with chemical bombs, rockets and artillery shells 387 times during the 8-years war by Iraq (1980鈥1988). More than 1,000 tons of sulfur mustard gas was used in the battlefields by the Iraqis against Iranian people. A high rate of morbidities occurred as the result of these attacks. This study aimed to evaluate the delayed toxic effects of sulfur mustard gas on Iranian victims. During a systematic search, a total of 193 (109 more relevant to the main aim) articles on...
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Abstract Sulphur mustard (SM) is a blistering agent that causes debilitating damage to the skin, eyes and respiratory system. In cases of severe exposure, immunodepletion can occur as well as death, due to secondary infections. The toxicity of SM is thought to be mediated in part by the alkylation of nucleic acids and proteins, although the exact mechanisms are not clear. In addition, although the first known use of SM was in military conflict nearly 100 years ago, there are still no effective t...
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Abstract Sulphur mustard (SM) is a blistering agent that has been used several times as a weapon during military conflict. Interest in this compound persists due to its ease of production and potential threat as an agent of warfare/terrorism. In addition, there are increasing reports of long-term health effects in individuals previously exposed to this compound, including an increased incidence of certain cancers. It is therefore important to elucidate the toxic mechanisms of SM and how the cell...
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INTRODUCTION Achillea tenuifolia Lam (AT) has several biological activities and medicinal properties. In this study, we elucidated the impact of the AT on anxiety-related behaviors, reproductive parameters, antioxidant capacity in male rats subjected to chronic restraint stress (CRS). METHODS 35 Wistar rats were divided into five groups: control, CRS-control (received normal saline) and three CRS-treated groups received AT extract (100, 150, and 200 mg/kg body weight) for 21 consequences days. T...
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#1Xi Cheng (National University of Defense Technology)H-Index: 1
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Abstract Sulfur mustard (SM) is a blister chemical warfare agent with severe cytotoxicity and genotoxicity. It can extensively alkylate important macromolecules in organisms, such as proteins, DNA, and lipids, and produce a series of metabolites, among which the characteristic ones can be used as biomarkers. The exact toxicological mechanisms of SM remain unclear but mainly involve the DNA lesions induced by alkylation and oxidative stress caused by glutathione depletion. Various methods have be...
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Background Epigenetic modification pattern is considered as a characteristic feature in blood malignancies. Modifications in the DNA methylation modulators are recurrent in lymphoma and leukemia, so that, the distinct methylation pattern defines different types of leukemia. Generally, the role of epigenetics is less understood and most investigations are focused on genetic abnormalities and cytogenic studies to develop novel treatments for patients with hematologic disorders. Recently, understan...
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Abstract Mustard vesicants, including sulfur mustard (2,2鈥-dichlorodiethyl sulfide, SM) and nitrogen mustard (bis(2-chloroethyl)methylamine, HN2) are cytotoxic blistering agents synthesized for chemical warfare. Because they contain highly reactive electrophilic chloroethyl side chains, they readily react with cellular macromolecules like DNA forming monofunctional and bifunctional adducts. By targeting DNA, mustards can compromise genomic integrity, disrupt the cell cycle, and cause mutations a...
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Abstract Nitrogen mustard (NM) is a highly reactive bifunctional alkylating agent that induces inflammation, edema and blistering in skin. An important mechanism mediating the action of NM and related mustards is oxidative stress. In these studies a modified murine patch-test model was used to analyze DNA damage and the antioxidant/stress response following NM exposure in isolated epidermis. NM (20鈥糾ol) was applied to glass microfiber filters affixed to a shaved dorsal region of skin of CD-1 mi...
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#1Yi Hua Jan (RU: Rutgers University)H-Index: 3
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Nitrogen mustard, mechlorethamine (bis(2-chloroethyl)methylamine; HN2), and sulfur mustard are potent vesicants that modify and disrupt cellular macromolecules including DNA leading to cytotoxicity and tissue injury. In many cell types, HN2 upregulates DNA damage signaling pathways including ataxia telangiectasia mutated (ATM), ataxia telangiectasia mutated- and Rad3-related (ATR) as well as DNA-dependent protein kinase (DNA-PK). In the present studies, we investigated crosstalk between the HN2-...
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Sulfur mustard (SM) is an extensive nucleophilic and alkylating agent that targets different tissues. The genotoxic property of SM is the most threatening effect, because it is associated with detrimental inflammations and susceptibility to several kinds of cancer. Moreover, SM causes a wide variety of adverse effects on DNA which result in accumulation of DNA adducts, multiple mutations, aneuploidies, and epigenetic aberrations in the genome. However, these adverse effects are still not known w...
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