Dietary quercetin inhibits 1,2-dimethylhydrazine–induced liver DNA damage without altering colon DNA damage or precancerous lesion formation in rats Ha-Na No a , Hoonjeong Kwon b , You-Gyoung Park b , Choong-Ill Cheon c , Jong-Sug Park d , Taesun Park e , Okezie I. Aruoma f , Mi-Kyung Sung a, ⁎ a Department of Food and Nutrition, Sookmyung Women's University, Seoul 140-742, South Korea b Department of Food and Nutrition, Seoul National University, Seoul 151-742, South Korea c Department of Biological Science, Sookmyung Women's University, Seoul 140-742, South Korea d Molecular Physiology and Biochemistry Division, National Institute of Agricultural Biotechnology, Suwon 441-707, South Korea e Department of Food and Nutrition, Yonsei University, Seoul 120-749, South Korea f Department of Pharmaceutical and Biomedical Sciences, Touro College of Pharmacy, New York, NY 10010, USA Received 4 December 2006; revised 14 July 2007; accepted 3 August 2007 Abstract Quercetin is a potent free radical–scavenging antioxidant exerting chemopreventive activity by reducing oxidative stresses. However, oxidized quercetin behaves as a prooxidant, which can lead to paradoxical effects. This study was conducted to investigate the effects of quercetin supplementation on 1,2-dimethylhydrazine (DMH)–induced oxidative DNA damage and precancerous lesion formation in the colon. Male Sprague-Dawley rats were randomized into 5 groups. The rats in groups 3, 4, and 5 were treated with DMH (30 mg/kg body weight IP), twice on weeks 2 and 3. The experimental diets were as follows: control diet (group 1), 2% quercetin diet (group 2), control diet (group 3), 0.2% quercetin diet (group 4), and 2% quercetin diet (group 5). The DMH-induced oxidative tissue damage was examined 24 hours after the first DMH injection, and the aberrant crypt foci formation was measured at week 12. The results show the following: (1) that DMH significantly increased the level of 8-hydroxyguanine (8-OH-Gua) in the liver, where the metabolic conversion of DMH occurs, but did not significantly change the level of 8-OH-Gua in the colon; (2) that both the 0.2% and 2% quercetin supplementation suppressed the extent of 8-OH-Gua formation in the liver; (3) that dietary quercetin did not affect the formation of aberrant crypt foci; and (4) that 2% quercetin supplementation only slightly increased the liver oxidative damage without statistical significance. These results indicate that quercetin may not be an effective anticarcinogen against DMH-induced colon cancer, where oxidative tissue damage is not a primary event in the formation of a precancerous region. The context of quercetin as a hepatoprotective agent, however, must be emphasized. © 2007 Elsevier Inc. All rights reserved. Keywords: Quercetin; Oxidative DNA damage; Colon cancer; Antioxidants; 1,2-Dimethylhydrazine; Colon-aberrant crypts; Rats 1. Introduction Epidemiological studies suggest that plant food con- sumption is negatively related to the risk of colon cancer [1]. Many protective effects of plant food have been attributed to Available online at www.sciencedirect.com Nutrition Research 27 (2007) 659 – 664 www.elsevier.com/locate/nutres ⁎ Corresponding author. Tel.: +82 2 710 9395; fax: +82 2 710 9395. E-mail address: mksung@sookmyung.ac.kr (M.-K. Sung). 0271-5317/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.nutres.2007.08.001