Dihydromethysticin (DHM) Blocks Tobacco Carcinogen 4-(Methyl...

来自 : 发布时间：2024-12-22

Dihydromethysticin (DHM) Blocks Tobacco Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-Induced O6-Methylguanine in a Manner Independent of the Aryl Hydrocarbon Receptor (AhR) Pathway in C57BL/6 Female Mice | Chemical Research in Toxicology Chem. Res. Toxicol.All Publications/WebsiteOR SEARCH CITATIONS Recently ViewedYou have not visited any articles yet, Please visit some articles to see contents here. RETURN TO ISSUEPREVArticleNEXTDihydromethysticin (DHM) Blocks Tobacco Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-Induced O6-Methylguanine in a Manner Independent of the Aryl Hydrocarbon Receptor (AhR) Pathway in C57BL/6 Female MiceSreekanth C. Narayanapillai†,Shang-Hsuan Lin†,Pablo Leitzman†,Pramod Upadhyaya‡,Carolyn J. Baglole§,andChengguo Xing*†‡∥View Author Information† Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States‡ Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States§ Meakins-Christie Laboratories, McGill University, Montreal, Québec, Canada∥ Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States*Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610. Phone: 352-294-8511. E-mail: [email protected]Cite this: Chem. Res. Toxicol. 2016, 29, 11, 1828–1834Publication Date (Web):October 11, 2016Publication History Received11 June 2016Published online21 October 2016Published inissue 21 November 2016https://doi.org/10.1021/acs.chemrestox.6b00203Copyright © 2016 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views337Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.Get e-AlertsAbstract4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a key carcinogen responsible for tobacco smoke-induced lung carcinogenesis. Among the types of DNA damage caused by NNK and its metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), O6-methylguanine (O6-mG) is likely the most carcinogen in A/J mice. Results of our previous studies showed that levels of O6-mG and other types of NNAL-derived DNA damage were preferentially reduced in the lung of female A/J mice upon dietary treatment with dihydromethysticin (DHM), a promising lung cancer chemopreventive agent from kava. Such a differential blockage may be mediated via an increased level of NNAL glucuronidation, thereby leading to its detoxification. The potential of the aryl hydrocarbon receptor (AhR) as an upstream target of DHM mediating these events was evaluated herein using Ahr+/– and Ahr–/– C57BL/6 female mice because DHM was reported as an AhR agonist. DHM (0.05, 0.2, and 1.0 mg/g of diet) and dihydrokavain (DHK, an inactive analogue, 1.0 mg/g of diet) were given to mice for 7 days, followed by a single intraperitoneal dose of NNK at 100 mg/kg of body weight. The effects of DHM on the amount of O6-mG in the lung, on the urinary ratio of glucuronidated NNAL (NNAL-Gluc) and free NNAL, and on CYP1A1/2 activity in the liver microsomes were analyzed. As observed in A/J mice, DHM treatment significantly and dose-dependently reduced the level of O6-mG in the target lung tissue, but there were no significant differences in O6-mG reduction between mice from Ahr+/– and Ahr–/– backgrounds. Similarly, in both strains, DHM at 1 mg/g of diet significantly increased the urinary ratio of NNAL-Gluc to free NNAL and CYP1A1/2 enzymatic activity in liver with no changes detected at lower DHM dosages. Because none of these effects of DHM were dependent on Ahr status, AhR clearly is not the upstream target for DHM.Supporting InformationARTICLE SECTIONSJump ToThe Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.chemrestox.6b00203.Confirmation of the Ahr status of lung and liver tissues from representative mice (PDF)tx6b00203_si_001.pdf (322.21 kb) Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html. Cited ByThis article is cited by 6 publications.Zhuo Qu, Lei Zhang, Ruilin Hou, Xueqin Ma, Jianqiang Yu, Wannian Zhang, Chunlin Zhuang. Exposure to a mixture of cigarette smoke carcinogens disturbs gut microbiota and influences metabolic homeostasis in A/J mice. Chemico-Biological Interactions 2021, 344 , 109496. https://doi.org/10.1016/j.cbi.2021.109496Tengfei Bian, Pedro Corral, Yuzhi Wang, Jordy Botello, Rick Kingston, Tyler Daniels, Ramzi G. Salloum, Edward Johnston, Zhiguang Huo, Junxuan Lu, Andrew C. Liu, Chengguo Xing. Kava as a Clinical Nutrient: Promises and Challenges. Nutrients 2020, 12 (10) , 3044. https://doi.org/10.3390/nu12103044Alena Liskova, Patrik Stefanicka, Marek Samec, Karel Smejkal, Pavol Zubor, Tibor Bielik, Kristina Biskupska-Bodova, Taeg Kyu Kwon, Jan Danko, Dietrich Büsselberg, Mariusz Adamek, Luis Rodrigo, Peter Kruzliak, Aleksandr Shleikin, Peter Kubatka. Dietary phytochemicals as the potential protectors against carcinogenesis and their role in cancer chemoprevention. Clinical and Experimental Medicine 2020, 20 , 173-190. https://doi.org/10.1007/s10238-020-00611-wYi Wang, Sreekanth C. Narayanapillai, Katelyn M. Tessier, Lori G. Strayer, Pramod Upadhyaya, Qi Hu, Rick Kingston, Ramzi G. Salloum, Junxuan Lu, Stephen S. Hecht, Dorothy K. Hatsukami, Naomi Fujioka, Chengguo Xing. The Impact of One-week Dietary Supplementation with Kava on Biomarkers of Tobacco Use and Nitrosamine-based Carcinogenesis Risk among Active Smokers. Cancer Prevention Research 2020, 13 , 483-492. https://doi.org/10.1158/1940-6207.CAPR-19-0501Antonio Celentano, Andrew Tran, Claire Testa, Krishen Thayanantha, William Tan‐Orders, Stephanie Tan, Mitali Syamal, Michael J. McCullough, Tami Yap. The protective effects of Kava (Piper Methysticum) constituents in cancers: A systematic review. Journal of Oral Pathology Medicine 2019, 48 , 510-529. https://doi.org/10.1111/jop.12900A. A. Alahmari, B. Sreekumar, V. Patel, M. Ashat, M. Alexandre, A. K. Uduman, E. O. Akinbiyi, A. Ceplenski, C. A. Shugrue, T. R. Kolodecik, N. Tashkandi, S. W. Messenger, G. E. Groblewski, F. S. Gorelick, E. C. Thrower, . Cigarette toxin 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces experimental pancreatitis through α7 nicotinic acetylcholine receptors (nAChRs) in mice. PLOS ONE 2018, 13 , e0197362. https://doi.org/10.1371/journal.pone.0197362Export articles to MendeleyGet article recommendations from ACS based on references in your Mendeley library.Export articles to MendeleyGet article recommendations from ACS based on references in your Mendeley library. Please note: If you switch to a different device, you may be asked to login again with only your ACS ID. Please note: If you switch to a different device, you may be asked to login again with only your ACS ID. Please note: If you switch to a different device, you may be asked to login again with only your ACS ID. Please login with your ACS ID before connecting to your Mendeley account.Login with ACS ID This website uses cookies to improve your user experience. By continuing to use the site, you are accepting our use of cookies. Read the ACS privacy policy. CONTINUE