This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Valinluck, V. Articles by Sowers, L. C. Search for Related Content PubMed PubMed Citation Articles by Valinluck, V. Articles by Sowers, L. C. Related Collections Cellular Pathobiology Cellular Pathobiology: DNA Damage and Stress Responses Tumor Biology Tumor Biology: Inflammation and Immune Escape

Inflammation-Mediated Cytosine Damage: A Mechanistic Link between Inflammation and the Epigenetic Alterations in Human Cancers

Department of Biochemistry and Microbiology, School of Medicine, Loma Linda University, Loma Linda, California

Requests for reprints: Lawrence C. Sowers, Biochemistry and Microbiology, Loma Linda University School of Medicine, Alumni Hall for Basic Sciences, Room 102, 11021 Campus Street, Loma Linda, CA 92354. Phone: 909-558-4480; Fax: 909-558-4035; E-mail: lsowers{at}llu.edu.

Aberrant methylation patterns have long been known to exist in the promoter regions of key regulatory genes in the DNA of tumor cells. However, the mechanisms by which these methylation patterns become altered during the transformation of normal cells to tumor cells have remained elusive. We have recently shown in in vitro studies that inflammation-mediated halogenated cytosine damage products can mimic 5-methylcytosine in directing enzymatic DNA methylation and in enhancing the binding of methyl-binding proteins whereas certain oxidative damage products inhibit both. We have therefore proposed that cytosine damage products could potentially interfere with normal epigenetic control by altering DNA-protein interactions critical for gene regulation and the heritable transmission of methylation patterns. These inflammation-mediated cytosine damage products may provide, in some cases, a mechanistic link between inflammation and cancer. [Cancer Res 2007;67(12):5583–6]