|
|
|
|
|
Robeena M. Aziz, Department of Environmental Health Sciences, Ohio State University, 300 W. 10th Ave, Room 1144, Columbus, OH 43220, (614) 293-3713, aziz.4@osu.edu, Ron Nines, College of Medicine/ Division of Hematology and Oncology, Ohio State University, 300 W. 10th Ave, Columbus, OH 43210, Tamaro Hudson, Environmental Health Sciences, Ohio State University, 300 W. 10th Ave, Columbus, OH 43210, and Gary D. Stoner, School of Public Health, Environmental Health Sciences, Ohio State University, 300 W10th. Ave. Room 1148, Columbus, OH 43212.
The rat esophagus is a useful model for human esophageal squamous cell carcinoma. Tumors can easily be induced in the rat esophagus by treatment of the rats with the nitrosamine carcinogen, N-nitrosomethylbenzylamine (NMBA). NMBA induces esophageal tumors in the rat when administered once weekly for 15 weeks or 3 times/week for 5 weeks at a dose of 0.25 mg/kg/injection. Also, NMBA is a selective carcinogen inducing tumors only in specific tissues such as the esophagus and nasal cavity. NMBA metabolism involves a series of reactions which eventually lead to the formation of an unstable carbonium ion that can directly affect DNA by methylating the O6 and/or N-7 positions of guanine. DFMO is an enzyme-activated irreversible inhibitor of ornithine decarboxylase, which is the rate-limiting enzyme in polyamine synthesis, and decreases intracellular levels of putrescine and spermidine in the skin and other vital tissues. In conjunction with the administration of model carcinogens, DFMO significantly reduced tumor incidence in several mammalian in vivo tests for chemopreventive activity. Past studies have shown DFMO to be an effective inhibitor of N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat esophagus when administered before, during and after carcinogen treatment. The main purpose of this study was to determine whether DFMO is associated with a significant reduction in rat esophageal tumorigenesis when administered in the diet following pre-initiation of animals with NMBA. At the end of the study, we found that DFMO reduced tumor multiplicity by 40% (p = 0.056). These data suggest that DFMO is a potentially useful chemopreventive agent in the rat esophagus.
Learning Objectives:
Keywords: Cancer, Cancer Prevention
Presenting author's disclosure statement:
I do not have any significant financial interest/arrangement or affiliation with any organization/institution whose products or services are being discussed in this session.