Carcinogenesis, Vol. 21, No. 2, 257-263,
February 2000
© 2000 Oxford University Press
Carcinogenesis |
Oxidative damage in an esophageal adenocarcinoma model with rats
Laboratory for Cancer Research, College of Pharmacy, Rutgers University, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA
Oxidative damage has long been related to carcinogenesis in human cancers and animal cancer models. Recently a rat esophageal adenocarcinoma (EAC) model was established in our laboratory by using esophagoduodenal anastomosis (EDA) plus iron supplementation. Our previous study suggested that iron supplementation enhanced inflammation and the production of reactive nitrogen species in the esophageal epithelium, which could contribute to esophageal adenocarcinogenesis. Here we further characterized oxidative damage in this model. We were particularly interested in how excess iron was deposited in the esophagus, and which cells were targeted by oxidative damage. Male Sprague–Dawley rats received iron supplementation (50 mg Fe/kg/month, i.p.) starting 4 weeks after EDA. The animals were killed at 11, 30 or 35 weeks after surgery. EAC appeared as early as week 11 after surgery, and increased over time, up to 60% at 35 weeks after surgery. All EACs were well-differentiated mucinous adenocarcinoma at the squamocolumnar junction. Iron deposition was found at the squamocolumnar junction and in the area with esophagitis. Esophageal iron overload could result from transient increase of blood iron after i.p. injection, and the overexpression of transferrin receptor in the premalignant columnar-lined esophagus (CLE) cells. Oxidative damage to DNA (8-hydroxy-2'-deoxyguanosine), protein (carbonyl content) and lipid (thiobarbituric acid reactive substance) in the esophagus was significantly higher than that of the non-operated control. CLE cells were believed to be the target cells of oxidative damage because they overexpressed heme oxygenase 1 and metallothionein, both known to be responsive to oxidative damage. We propose that oxidative damage plays an important role in the formation of EAC in the EDA model, and a similar situation may occur in humans with gastroesophageal reflux and iron over-nutrition.
Abbreviations: 8-OH-dG, 8-hydroxy-2'-deoxyguanosine; CLE, columnar-lined esophagus; EAC, esophageal adenocarcinoma; EDA, esophagoduodenal anastomosis; HO1, heme oxygenase 1; MT, metallothionein; ROS, reactive oxygen species; TBARS, thiobarbituric acid reactive substance; TfR, transferrin receptor.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. A. Feagins, H. Y. Zhang, X. Zhang, K. Hormi-Carver, T. Thomas, L. S. Terada, S. J. Spechler, and R. F. Souza Mechanisms of oxidant production in esophageal squamous cell and Barrett's cell lines Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G411 - G417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Boult, K. Roberts, M. J. Brookes, S. Hughes, J. P. Bury, S. S. Cross, G. J. Anderson, R. Spychal, T. Iqbal, and C. Tselepis Overexpression of Cellular Iron Import Proteins Is Associated with Malignant Progression of Esophageal Adenocarcinoma Clin. Cancer Res., January 15, 2008; 14(2): 379 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Risques, T. L. Vaughan, X. Li, R. D. Odze, P. L. Blount, K. Ayub, J. L. Gallaher, B. J. Reid, and P. S. Rabinovitch Leukocyte Telomere Length Predicts Cancer Risk in Barrett's Esophagus Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2649 - 2655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C.G. Martin, Q. Liu, J. M. Wo, M. B. Ray, and Y. Li Chemoprevention of Carcinogenic Progression to Esophageal Adenocarcinoma by the Manganese Superoxide Dismutase Supplementation Clin. Cancer Res., September 1, 2007; 13(17): 5176 - 5182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, J. M. Wo, R. R. Su, M. B. Ray, and R. C. G. Martin Alterations in Manganese Superoxide Dismutase Expression in the Progression From Reflux Esophagitis to Esophageal Adenocarcinoma Ann. Surg. Oncol., July 1, 2007; 14(7): 2045 - 2055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Dvorak, C. M Payne, M. Chavarria, L. Ramsey, B. Dvorakova, H. Bernstein, H. Holubec, R. E Sampliner, N. Guy, A. Condon, et al. Bile acids in combination with low pH induce oxidative stress and oxidative DNA damage: relevance to the pathogenesis of Barrett's oesophagus Gut, June 1, 2007; 56(6): 763 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Erbil, U. Turkoglu, U. Barbaros, E. Balik, V. Olgac, H. Kaya, and B. Cimsit Oxidative Damage in an Experimentally Induced Gastric and Gastroduodenal Reflux Model Surgical Innovation, September 1, 2005; 12(3): 219 - 225. [Abstract] [PDF]
|
|
|
|
|
|
J. R. Olliver, L. J. Hardie, Y. Gong, S. Dexter, D. Chalmers, K. M. Harris, and C. P. Wild Risk Factors, DNA Damage, and Disease Progression in Barrett's Esophagus Cancer Epidemiol. Biomarkers Prev., March 1, 2005; 14(3): 620 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kumagai, K.-i. Mukaisho, H. Sugihara, K. Miwa, G. Yamamoto, and T. Hattori Thioproline inhibits development of esophageal adenocarcinoma induced by gastroduodenal reflux in rats Carcinogenesis, May 1, 2004; 25(5): 723 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Yoshida, Y. Ogawa, I. Mori, A. Nakata, R. Wang, S. Ueno, I. Shioji, and N. Hisanaga Associations between oxidative stress levels and total duration of engagement in jobs with exposure to fly ash among workers at municipal solid waste incinerators Mutagenesis, November 1, 2003; 18(6): 533 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Chen, N. Li, S. Wang, N. Wu, J. Hong, X. Jiao, M. J. Krasna, D. G. Beer, and C. S. Yang Leukotriene A4 Hydrolase in Rat and Human Esophageal Adenocarcinomas and Inhibitory Effects of Bestatin J Natl Cancer Inst, July 16, 2003; 95(14): 1053 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, Y. Ding, C.-G. Liu, S. Mikhail, and C. S. Yang Overexpression of glucose-regulated protein 94 (Grp94) in esophageal adenocarcinomas of a rat surgical model and humans Carcinogenesis, January 1, 2002; 23(1): 123 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kato, M. Kobune, T. Nakamura, G. Kuroiwa, K. Takada, R. Takimoto, Y. Sato, K. Fujikawa, M. Takahashi, T. Takayama, et al. Normalization of Elevated Hepatic 8-Hydroxy-2'-Deoxyguanosine Levels in Chronic Hepatitis C Patients by Phlebotomy and Low Iron Diet Cancer Res., December 1, 2001; 61(24): 8697 - 8702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Y Oh, J S Lee, B O Ahn, H Cho, W B Kim, Y B Kim, Y J Surh, S W Cho, K M Lee, and K B Hahm Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats Gut, September 1, 2001; 49(3): 364 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen and C. S. Yang Esophageal adenocarcinoma: a review and perspectives on the mechanism of carcinogenesis and chemoprevention Carcinogenesis, August 1, 2001; 22(8): 1119 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fein, K.-H. Fuchs, H. Stopper, S. Diem, and M. Herderich Duodenogastric reflux and foregut carcinogenesis: analysis of duodenal juice in a rodent model of cancer Carcinogenesis, November 1, 2000; 21(11): 2079 - 2084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, S. S. Mikhail, Y. W. Ding, G.-y. Yang, F. Bondoc, and C. S. Yang Effects of vitamin E and selenium supplementation on esophageal adenocarcinogenesis in a surgical model with rats Carcinogenesis, August 1, 2000; 21(8): 1531 - 1536. [Abstract] [Full Text] [PDF]
|
|