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