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 HighWire Citing Articles via Google Scholar Google Scholar Articles by El-Bayoumy, K. Articles by Wynder, E. L. Search for Related Content PubMed PubMed Citation Articles by El-Bayoumy, K. Articles by Wynder, E. L.

Increased Expression of Cyclooxygenase-2 in Rat Lung Tumors Induced by the Tobacco-specific Nitrosamine 4-(Methylnitrosamino)-4-(3-pyridyl)-1-butanone

The Impact of a High-Fat Diet¹

American Health Foundation, Valhalla, New York 10595

Aberrant or excessive expression of cyclooxygenase (COX)-2 has been implicated in the pathogenesis of many disease processes, including carcinogenesis. COX-2 expression was immunohistochemically examined in archival samples (D. Hoffmann et al., Cancer Res., 53: 2758–2761, 1993) of lung neoplasms (adenomas, adenocarcinomas, and adenosquamous carcinomas) induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in male F344 rats that had been fed either a semipurified AIN-76A diet with high-fat (HF; 23.5% corn oil) or low-fat (LF; 5% corn oil) content. The intensity and extent of COX-2 positivity was graded from 0 (undetectable or negligible expression) to grades 1 (<30% expression), 2 (30–60% expression), 3 (60–90% expression), and 4 (>90% expression). The scoring criteria were similar to those used with specimens from human lung cancers (T. Hida et al., Cancer Res., 58: 3761–3764, 1998). In group 1 (NNK plus HF diet), adenomas, adenocarcinomas, and adenosquamous carcinomas were of mean grades 2, 3, and 4, respectively; in group 2 (NNK plus LF diet), the corresponding mean grades were 1, 1, and 3. Although control rats, given HF (group 3) or LF (group 4) diets but no NNK, developed spontaneous lung tumors, the expression of COX-2 was either negligible (one adenoma of grade 0 in group 3) or of a very low grade (one adenocarcinoma of grade 1 in group 4). In addition, the latency of the tumors in the peripheral lung in assays with NNK is significantly shorter in rats maintained on the HF diet than in those on LF diet. COX-2 expression was not evident in normal lung tissues. We report here for the first time that NNK induces increasingly higher levels of COX-2 expression with progressive stages of lung tumorigenesis when rats are fed the HF diet. The increase in COX-2 expression may be associated with the development of lung tumors induced by NNK. This well-defined animal model is valuable for studying modulation of COX-2 expression in lung carcinogenesis by various factors, including dietary components.

This article has been cited by other articles:

				S. I. Chang, K. El-Bayoumy, I. Sinha, N. Trushin, B. Stanley, B. Pittman, and B. Prokopczyk 4-(Methylnitrosamino)-I-(3-Pyridyl)-1-Butanone Enhances the Expression of Apolipoprotein A-I and Clara Cell 17-kDa Protein in the Lung Proteomes of Rats Fed a Corn Oil Diet but not a Fish Oil Diet Cancer Epidemiol. Biomarkers Prev., February 1, 2007; 16(2): 228 - 235. [Abstract] [Full Text] [PDF]

				S. Razani-Boroujerdi and M. L. Sopori Early Manifestations of NNK-Induced Lung Cancer: Role of Lung Immunity in Tumor Susceptibility Am. J. Respir. Cell Mol. Biol., January 1, 2007; 36(1): 13 - 19. [Abstract] [Full Text] [PDF]

				J. Ding, J. Li, C. Xue, K. Wu, W. Ouyang, D. Zhang, Y. Yan, and C. Huang Cyclooxygenase-2 Induction by Arsenite Is through a Nuclear Factor of Activated T-cell-dependent Pathway and Plays an Antiapoptotic Role in Beas-2B Cells J. Biol. Chem., August 25, 2006; 281(34): 24405 - 24413. [Abstract] [Full Text] [PDF]

				C. A. Martey, S. J. Pollock, C. K. Turner, K. M. A. O'Reilly, C. J. Baglole, R. P. Phipps, and P. J. Sime Cigarette smoke induces cyclooxygenase-2 and microsomal prostaglandin E2 synthase in human lung fibroblasts: implications for lung inflammation and cancer Am J Physiol Lung Cell Mol Physiol, November 1, 2004; 287(5): L981 - L991. [Abstract] [Full Text] [PDF]

				A. F. Gazdar, K. Miyajima, J. Reddy, U. G. Sathyanarayana, H. Shigematsu, M. Suzuki, T. Takahashi, and N. Shivapurkar Molecular Targets for Cancer Therapy and Prevention Chest, May 1, 2004; 125(5_suppl): 97S - 101S. [Abstract] [Full Text] [PDF]

				H.-Y. Lee, Y.-A. Suh, J. W. Kosmeder, J. M. Pezzuto, W. K. Hong, and J. M. Kurie Deguelin-Induced Inhibition of Cyclooxygenase-2 Expression in Human Bronchial Epithelial Cells Clin. Cancer Res., February 1, 2004; 10(3): 1074 - 1079. [Abstract] [Full Text] [PDF]

				P. S. Carlton, R. Gopalakrishnan, A. Gupta, B. W. Liston, S. Habib, M. A. Morse, and G. D. Stoner Piroxicam Is an Ineffective Inhibitor of N-Nitrosomethylbenzylamine-induced Tumorigenesis in the Rat Esophagus Cancer Res., August 1, 2002; 62(15): 4376 - 4382. [Abstract] [Full Text] [PDF]

				S. S. Hecht, S. G. Carmella, M. Ye, K.-a. Le, J. A. Jensen, C. L. Zimmerman, and D. K. Hatsukami Quantitation of Metabolites of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone after Cessation of Smokeless Tobacco Use Cancer Res., January 1, 2002; 62(1): 129 - 134. [Abstract] [Full Text] [PDF]

				T. Utsunomiya, M. Shimada, T. Rikimaru, K. Sugimachi, K.-I. Ohkura, S. Kaku, K. Yamada, and K.-I. Taguchi Correspondence re: M. Kondo et al., Increased Expression of COX-2 in Nontumor Liver Tissue Is Associated with Shorter Disease-free Survival in Patients with Hepatocellular Carcinoma. Clin. Cancer Res., 5: 4005-4012, 1999. Clin. Cancer Res., December 1, 2000; 6(12): 4965 - 4966. [Abstract] [Full Text]

				N. Rioux and A. Castonguay The induction of cyclooxygenase-1 by a tobacco carcinogen in U937 human macrophages is correlated to the activation of NF-{kappa}B Carcinogenesis, September 1, 2000; 21(9): 1745 - 1751. [Abstract] [Full Text] [PDF]

				A. K. Bauer, L. D. Dwyer-Nield, and A. M. Malkinson High cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) contents in mouse lung tumors Carcinogenesis, April 1, 2000; 21(4): 543 - 550. [Abstract] [Full Text] [PDF]