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Unformatted text preview: http://het.sagepub.com Human & Experimental Toxicology DOI: 10.1191/096032700701546442 2000; 19; 543 Hum Exp Toxicol J E Klaunig, L M Kamendulis and Yong Xu Epigenetic mechanisms of chemical carcinogenesis http://het.sagepub.com/cgi/content/abstract/19/10/543 The online version of this article can be found at: Published by: http://www.sagepublications.com can be found at: Human & Experimental Toxicology Additional services and information for http://het.sagepub.com/cgi/alerts Email Alerts: http://het.sagepub.com/subscriptions Subscriptions: http://www.sagepub.com/journalsReprints.nav Reprints: http://www.sagepub.com/journalsPermissions.nav Permissions: http://het.sagepub.com/cgi/content/refs/19/10/543 SAGE Journals Online and HighWire Press platforms): (this article cites 128 articles hosted on the Citations 2000 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at MICHIGAN STATE UNIV LIBRARIES on December 21, 2007 http://het.sagepub.com Downloaded from Human & ExperimentalToxicology(2000)19, 543-555 c 2000AmoldAllrightsreserved0960-3271/00 www.arnoldpublishers.comrAournals Epigenetic mechanisms ofchemical a a carcinogenesis JEKlaunig*, LM Kamendulis and Yong Xu Division ofToxicology, Department of Pharmacologyand Toxicology, Indiana University, Indianapolis, Indiana, USA Chemicallyinducedcancer isa multi-stepprocess involving damagetothegenome initiallyfollowedbyclonalexpansion oftheDNA damagedcelleventuallyleadingtoa neoplasm. Chemicalcarcinogenshavebeenshowntoimpactatallofthe stagesofthetumorigenesisprocess. Ithasbecome apparent thatchemicalandphysicalagentsthatinducecancer m a y do so throughseveraldifferentcellular andmolecularmechan- isms. Epigenetic (nongenotoxic) chemical carcinogens are those agents that function to induce tumor formation by mechanisms exclusiveofdirectmodification or damageto DNA. Theseagents appear tomodulatecellgrowthand cell death and exhibit dose response relationships between exposure and tumor formation. Theexactand/orexclusive mechanisms by whichthese agentsfunctionhavenotbeen established,however,changesincellgrowthregulation and gene expression are importantto tumor formation. This reviewfocusesonseveral potential mechanismsandcellular processes thatmay be involvedinnongenotoxicchemical carcinogenesis. Human & Experimental Toxicology (2000) 19, 543-555. Keywords: epigenetic; carcinogenesis; cell proliferation; gene expression Overview Linkage between exposure to chemicals and the induction of cancer in rodents has been well established.A cause- and- effectanddose- responsive relationship has been established between chemical carcinogen exposure andsubsequentdevelopmentof neoplasia.Investigatorsinthemid-twentieth century establishedthata multistagedprocess was involvedin cancer development. Subsequent work showed that chemical carcinogens can function at several ofthe stages of the tumorigenesis process. Ithas become apparent that chemical and physical agents that induce cancer...
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