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 Homma, Y. Articles by Oyasu, R. Search for Related Content PubMed PubMed Citation Articles by Homma, Y. Articles by Oyasu, R.

Inhibition of Carcinogenesis by -Difluoromethylornithine in Heterotopically Transplanted Rat Urinary Bladders¹

Departments of Pathology [Y. H., S. O., I. N., R. O.] and Pharmacology [J. S.], Northwestern University Medical School and Northwestern University Cancer Center, Chicago, Illinois 60611

Inhibitory effects of -difluoromethylornithine (DFMO) on urinary bladder carcinogenesis were examined using the heterotopically transplanted rat urinary bladder (HTB) model. Male Fischer rats with an HTB were arbitrarily divided into four groups. Group 1 rats received into the HTBs 0.25 mg of N-methyl-N-nitrosourea (MNU) once a week for 3 weeks, followed by instillation twice a week of 0.5 ml of 2% DFMO dissolved in normal rat urine. Group 2 rats received the same amount of MNU, followed by instillation of urine without DFMO. Group 3 rats received a single dose of 0.25 mg of MNU, followed by instillation twice a week of urine containing 2% DFMO. Group 4 rats were treated as those in Group 3 but without DFMO. At 8, 14, and 20 weeks after the last MNU administration, urothelial polyamine levels and [³H] thymidine incorporation by the urothelium of HTBs were determined in nine rats of Groups 1 and 2. The remaining animals of Groups 1 and 2 were killed 25 weeks after the beginning of MNU injection, while those of Groups 3 and 4, 30 weeks after the MNU treatment. The contents of 3 polyamines (putrescine, spermidine, and spermine) in urothelial cells were significantly lower in Group 1 as compared with Group 2. The incidences of carcinoma were significantly lower in the groups treated with DFMO (p < 0.001, Group 1 versus Group 2; p < 0.005, Group 3 versus Group 4). These observations indicate that administration of DFMO inhibits (or retards) bladder carcinogenesis in HTBs. A possible mechanism for this effect is suppression of polyamine biosynthesis and proliferation of bladder epithelial cells.

¹ This investigation was supported by NIH Grant CA 33511 from the National Cancer Institute.

² Present address: Department of Urology, Tohoku University, School of Medicine, Sendai, Japan.

³ To whom requests for reprints should be addressed.

Received 8/13/84. Accepted 11/ 2/84.

This article has been cited by other articles:

				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]