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 Tempero, M. A. Articles by Zetterman, R. K. Search for Related Content PubMed PubMed Citation Articles by Tempero, M. A. Articles by Zetterman, R. K.

Chemoprevention of Mouse Colon Tumors with Difluoromethylornithine during and after Carcinogen Treatment¹

Omaha Veterans Administration Medical Center, Omaha, Nebraska 68105 [M. A. T., K. K., R. K. Z.]; and the Department of Internal Medicine, Sections of Oncology/Hematology [M. A. T.] and Gastroenterology [R. K. Z.], University of Nebraska Medical Center, Omaha, Nebraska, 68105; and The University of Texas M.D. Anderson Cancer Center, Department of General Surgery² Houston, Texas, Box 107, 77030 [K. N.]

-Difluoromethylornithine (DFMO) treatment has been shown to modify carcinogenesis in many experimental tumor models, including skin, breast, and colon. This study was designed to determine whether DFMO treatment can inhibit experimental mouse colon tumors after carcinogen treatment and whether an associated effect of DFMO on cell proliferation in colon mucosa occurs. Male CD₁ mice (40 per group) received dimethylhydrazine (30 mg/kg/week x 6 weeks, s.c.) and various schedules of DFMO, 1% in drinking water: Group A, none; Group B, following dimethylhydrazine treatment; Group C, during dimethylhydrazine treatment; and Group D, continuously throughout the study. Measurements of RBC polyamine levels showed that DFMO treatment ablated putrescine levels and confirmed that a systemic biological effect was achieved. Analysis of tumor data showed a significant inhibitory effect of DFMO treatment on colon tumor (adenomas and adenocarcinomas) incidence in Groups B (24%) and D (20%) compared to control Group A (52%, P < 0.05 A versus B, P < 0.02 A versus D) and on squamous cell carcinomas of the anus in all groups (P < 0.001 A versus B, P < 0.05 A versus C, A versus D). No consistent effect of DFMO treatment on cell proliferation in colon mucosa was identified. This study supports the hypothesis that DFMO treatment alters events in the postinitiation phases of mouse colon tumorigenesis.

¹ Supported by a grant from the Veterans Administration Merit Review.

² To whom requests for reprints should be addressed, at Associate Professor of Medicine, University of Nebraska Medical Center, 42nd and Dewey, Omaha, NE 68105-1065.

Received 1/ 6/89. Revised 7/11/89. Accepted 8/ 7/89.

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]

				P. P. Carbone, J. A. Douglas, J. Thomas, K. Tutsch, M. Pomplun, M. Hamielec, and D. Pauk Bioavailability Study of Oral Liquid and Tablet Forms of {{alpha}}-Difluoromethylornithine Clin. Cancer Res., October 1, 2000; 6(10): 3850 - 3854. [Abstract] [Full Text]

				R. F. Jacoby, C. E. Cole, K. Tutsch, M. A. Newton, G. Kelloff, E. T. Hawk, and R. A. Lubet Chemopreventive Efficacy of Combined Piroxicam and Difluoromethylornithine Treatment of Apc Mutant Min Mouse Adenomas, and Selective Toxicity against Apc Mutant Embryos Cancer Res., April 1, 2000; 60(7): 1864 - 1870. [Abstract] [Full Text]

				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]

				J. M. Arbeit, R. R. Riley, B. Huey, C. Porter, G. Kelloff, R. Lubet, J. M. Ward, and D. Pinkel Difluoromethylornithine Chemoprevention of Epidermal Carcinogenesis in K14-HPV16 Transgenic Mice Cancer Res., August 1, 1999; 59(15): 3610 - 3620. [Abstract] [Full Text] [PDF]