Modulation of DNA hypomethylation as a surrogate endpoint biomarker for chemoprevention of colon cancer
Article first published online: 23 JAN 2004
Copyright © 2004 Wiley-Liss, Inc.
Volume 39, Issue 2, pages 79–84, February 2004
How to Cite
Tao, L., Wang, W., Kramer, P. M., Lubet, R. A., Steele, V. E. and Pereira, M. A. (2004), Modulation of DNA hypomethylation as a surrogate endpoint biomarker for chemoprevention of colon cancer. Mol. Carcinog., 39: 79–84. doi: 10.1002/mc.20003
- Issue published online: 23 JAN 2004
- Article first published online: 23 JAN 2004
- Manuscript Accepted: 7 NOV 2003
- Manuscript Received: 1 AUG 2003
- colon tumors;
- DNA hypomethylation
Surrogate end-point biomarkers are being developed as indicators of the efficacy of chemopreventive agents. These biomarkers are molecular and biological end-points that can be modulated by chemopreventive agents in accordance with their efficacy to prevent cancer. DNA hypomethylation is a common alteration found in colon tumors that has the potential of being modulated by chemopreventive agents and thus being useful as a surrogate end-point biomarker. Agents that were either effective or ineffective in preventing colon cancer were evaluated for the ability to modulate DNA hypomethylation in azoxymethane-induced colon tumors in male F344 rats. DNA methylation was determined by Dot Blot Analysis using a mouse monoclonal anti-5-methylcytosine antibody. Colon tumors had a 70% reduction in DNA methylation relative to normal colonic mucosa. DNA methylation in the tumors was increased by 7 days of treatment with agents that have been shown to prevent colon cancer (calcium chloride, α-diflouromethylornithine [DFMO], piroxicam, and sulindac), whereas agents shown not to prevent colon cancer in rats (low dose aspirin, 2-carboxyphenyl retinamide [2-CPR], quercetin, 9-cis retinoic acid, and rutin) did not increase DNA methylation. The results suggest that the ability to reverse the DNA hypomethylation in colon tumors could be useful as a surrogate end-point biomarker for chemoprevention of colon cancer. © 2004 Wiley-Liss, Inc.