{"title":"An LC-MS/MS Method for the Quantification of Tobacco-Specific Carcinogen Protein Adducts","authors":"Breanne Freeman, and , Chengguo Xing*, ","doi":"10.1021/acs.chemrestox.5c00149","DOIUrl":null,"url":null,"abstract":"<p >4-(Methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its major metabolite 4-(methylnitrosamino)-l-(3-pyridine)-l-butanol (NNAL) are tobacco-specific lung carcinogens. Methods have been developed to quantify NNK- and NNAL-specific DNA adducts in preclinical samples but are not feasible to translation due to limited access to target tissues for sufficient DNA. In addition, NNAL-specific DNA or protein adducts have never been detected in clinical samples, which are critical to assess the physiological relevance of NNAL bioactivation and carcinogenesis. We herein reported a highly sensitive and specific LC-MS/MS method to quantify the hydrolyzed product, 1-(3-pyridyl)-1,4-butanediol (PBD), from NNAL-induced protein adduct. This method was applied to a variety of biological samples to assess tobacco exposure and NNAL bioactivation.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 9","pages":"1455–1459"},"PeriodicalIF":3.8000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical Research in Toxicology","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.chemrestox.5c00149","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
4-(Methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its major metabolite 4-(methylnitrosamino)-l-(3-pyridine)-l-butanol (NNAL) are tobacco-specific lung carcinogens. Methods have been developed to quantify NNK- and NNAL-specific DNA adducts in preclinical samples but are not feasible to translation due to limited access to target tissues for sufficient DNA. In addition, NNAL-specific DNA or protein adducts have never been detected in clinical samples, which are critical to assess the physiological relevance of NNAL bioactivation and carcinogenesis. We herein reported a highly sensitive and specific LC-MS/MS method to quantify the hydrolyzed product, 1-(3-pyridyl)-1,4-butanediol (PBD), from NNAL-induced protein adduct. This method was applied to a variety of biological samples to assess tobacco exposure and NNAL bioactivation.
期刊介绍：
Chemical Research in Toxicology publishes Articles, Rapid Reports, Chemical Profiles, Reviews, Perspectives, Letters to the Editor, and ToxWatch on a wide range of topics in Toxicology that inform a chemical and molecular understanding and capacity to predict biological outcomes on the basis of structures and processes. The overarching goal of activities reported in the Journal are to provide knowledge and innovative approaches needed to promote intelligent solutions for human safety and ecosystem preservation. The journal emphasizes insight concerning mechanisms of toxicity over phenomenological observations. It upholds rigorous chemical, physical and mathematical standards for characterization and application of modern techniques.
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