Chengcheng Liao, Jiangning Zhao, Subodh Kumar, Chandraditya Chakraborty, Srikanth Talluri, Nikhil C Munshi, Masood A Shammas
{"title":"RAD51 Inhibitor Reverses Etoposide-Induced Genomic Toxicity and Instability in Esophageal Adenocarcinoma Cells.","authors":"Chengcheng Liao, Jiangning Zhao, Subodh Kumar, Chandraditya Chakraborty, Srikanth Talluri, Nikhil C Munshi, Masood A Shammas","doi":"10.46439/toxicology.2.006","DOIUrl":"https://doi.org/10.46439/toxicology.2.006","url":null,"abstract":"<p><strong>Aim: </strong>In normal cells, homologous recombination (HR) is strictly regulated and precise and plays an important role in preserving genomic integrity by accurately repairing DNA damage. RAD51 is the recombinase which mediates homologous base pairing and strand exchange during DNA repair by HR. We have previously reported that HR is spontaneously elevated (or dysregulated) in esophageal adenocarcinoma (EAC) and contributes to ongoing genomic changes and instability. The purpose of this study was to evaluate the impact of RAD51 inhibitor on genomic toxicity caused by etoposide, a chemotherapeutic agent.</p><p><strong>Methods: </strong>EAC cell lines (FLO-1 and OE19) were cultured in the presence of RAD51 inhibitor and/or etoposide, and impact on cell viability, apoptosis and genomic integrity/stability investigated. Genomic integrity/stability was monitored by evaluating cells for γ-H2AX (a marker for DNA breaks), phosphorylated RPA32 (a marker of DNA end resection which is a distinct step in the initiation of HR) and micronuclei (a marker of genomic instability).</p><p><strong>Results: </strong>Treatment with etoposide, a chemotherapeutic agent, was associated with marked genomic toxicity (as evident from increase in DNA breaks) and genomic instability in both EAC cell lines. Consistently, the treatment was also associated with apoptotic cell death. A small molecule inhibitor of RAD51 increased cytotoxicity while reducing genomic toxicity and instability caused by etoposide, in both EAC cell lines.</p><p><strong>Conclusion: </strong>RAD51 inhibitors have potential to increase cytotoxicity while reducing harmful genomic impact of chemotherapy.</p>","PeriodicalId":8227,"journal":{"name":"Archives of clinical toxicology","volume":"2 1","pages":"3-9"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38412340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Medicinal Poisons","authors":"V. Vaswani, A. Hashim","doi":"10.46439/toxicology.1.002","DOIUrl":"https://doi.org/10.46439/toxicology.1.002","url":null,"abstract":"There is great variation in the drugs prescribed, used and most importantly available to the public in different countries. In many countries there are strict controls on the supply of drugs but many potentially lethal compounds are still available to the public without prescription in the shops. Where drugs are easily available they are by far the most common method of suicide and suicidal gestures. The subject has expanded so greatly that it properly belongs in the field of clinical toxicology rather than legal medicine [1].","PeriodicalId":8227,"journal":{"name":"Archives of clinical toxicology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86558647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Determination of Pregabalin in Tissues and Fluids by Using GC","authors":"AM Elessawy, RH AbdelElaziz, Ahmed MA Shihata","doi":"10.46439/toxicology.1.003","DOIUrl":"https://doi.org/10.46439/toxicology.1.003","url":null,"abstract":"Pregabalin is an antiepileptic and analgesic drug, commercialized under the name of Lyrica and other names, generally used to treat neuropathic pain. The determination of pregabalin was quantified in tissues and fluids samples by using Gas chromatography coupled with mass spectrometry, isolation and precipitation protein by Ammonium Sulphate method. The limit of detection (LOD) is 200 ng and the limit of quantification (LOQ) in is 400 ng. Ibuprofen was used as internal standard, this methods has been applied in two cases of pregabalin.","PeriodicalId":8227,"journal":{"name":"Archives of clinical toxicology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80397656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxicity of Anticancer Therapies","authors":"","doi":"10.46439/toxicology.1.004","DOIUrl":"https://doi.org/10.46439/toxicology.1.004","url":null,"abstract":"","PeriodicalId":8227,"journal":{"name":"Archives of clinical toxicology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75624491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter from the Founding Editor Masood A Shammas","authors":"","doi":"10.46439/toxicology.1.001","DOIUrl":"https://doi.org/10.46439/toxicology.1.001","url":null,"abstract":"","PeriodicalId":8227,"journal":{"name":"Archives of clinical toxicology","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78278368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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