This Article 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 Kingsnorth, A. N. Articles by Malt, R. A. Search for Related Content PubMed PubMed Citation Articles by Kingsnorth, A. N. Articles by Malt, R. A.

Inhibition of Ornithine Decarboxylase with 2-Difluoromethylornithine: Reduced Incidence of Dimethylhydrazine-induced Colon Tumors in Mice¹

Surgical Services, Shriners Burns Institute and Massachusetts General Hospital, and Department of Surgery, Harvard Medical School, Boston, Massachusetts 02114 [A. N. K., W. W. K. K., R. A. M.]; Merrell Dow Research Center, Cincinnati Ohio 45215 [K. A. D., P. P. M.]; and Department of Pathology, Berkshire Medical Center, Pittsfield, Massachusetts 01201 [J. S. R.]

2-Difluoromethylornithine (DFMO) was administered to 1,2-dimethylhydrazine (DMH)-treated mice to reduce colonic polyamine levels and mucosal hyperplasia. Mice received 1% DFMO in drinking water throughout the experiment and were given injections of DMH (20 mg/kg) weekly for 28 weeks. DFMO inactivated 93% of colonic ornithine decarboxylase activity. Although DMH treatment did not induce colonic ornithine decarboxylase activity by Week 28, the putrescine content was increased 31% in DMH-treated mice (p < 0.01). Concurrent treatment with DFMO depressed putrescine content (42 to 63%) and spermidine content (27 to 38%), but it increased spermine content (18 to 22%). At Week 28 of treatment with DMH alone, RNA content was increased 8.6% (p < 0.01), DNA content 10% (p < 0.01), DNA specific activity 24% (p < 0.01), and crypt depth 20% (p < 0.01), but not in mice receiving DMH and DFMO. At 28 weeks, 13 of 17 mice (76%) treated with DMH alone had histologically confirmed colon cancers; of mice treated with DMH and DFMO, two of 18 (11%) had colonic tumors. Throughout the experiment, 50 colon cancers developed in 16 DMH-treated mice (mean, 3.12 tumors/mouse); three mice treated with DMH and DFMO developed three colon cancers total (p < 0.001). Reduction of colonic polyamine levels after DFMO treatment prevents proliferative changes induced by DMH and reduces the incidence of tumors.

¹ Supported by the Stanley Thomas Johnson Foundation.

² To whom requests for reprints should be addressed, at Massachusetts General Hospital, Boston, Mass. 02114.

Received 8/16/82. Accepted 3/ 1/83.

This article has been cited by other articles:

				F. L. Meyskens Jr. American Society of Preventive Oncology Distinguished Career Achievement Lecture 2006--Enjoy the Journey: The Long and Winding Road of Chemoprevention Agent Development. Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2038 - 2041. [Full Text] [PDF]

				J. E. Green, M.-A. Shibata, E. Shibata, R. C. Moon, M. R. Anver, G. Kelloff, and R. Lubet 2-Difluoromethylornithine and Dehydroepiandrosterone Inhibit Mammary Tumor Progression but not Mammary or Prostate Tumor Initiation in C3(1)/SV40 T/t-antigen Transgenic Mice Cancer Res., October 1, 2001; 61(20): 7449 - 7455. [Abstract] [Full Text] [PDF]

				R. E. Rudolph, T. L. Vaughan, B. E. Storer, R. C. Haggitt, P. S. Rabinovitch, D. S. Levine, and B. J. Reid Effect of Segment Length on Risk for Neoplastic Progression in Patients with Barrett Esophagus Ann Intern Med, April 18, 2000; 132(8): 612 - 620. [Abstract] [Full Text] [PDF]

				H. Geng, P. H. Naylor, J. Dosescu, M. Skunca, A. P.N. Majumdar, and J. A. Moshier TGF{alpha} is required for full expression of the transformed growth phenotype of NIH 3T3 cells overexpressing ornithine decarboxylase Carcinogenesis, April 1, 2000; 21(4): 567 - 572. [Abstract] [Full Text] [PDF]

				S. H. Erdman, N. A. Ignatenko, M. B. Powell, K. A. Blohm-Mangone, H. Holubec, J. M. Guillen-Rodriguez, and E. W. Gerner APC-dependent changes in expression of genes influencing polyamine metabolism, and consequences for gastrointestinal carcinogenesis, in the Min mouse Carcinogenesis, September 1, 1999; 20(9): 1709 - 1713. [Abstract] [Full Text] [PDF]