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Normal and Malignant Human Urothelium: In Vitro Response to Blockade of Polyamine Synthesis and Interconversion¹

Departments of Surgery [E. M. M., P. H.] and Human Oncology [E. M. M., C. A. R.], University of Wisconsin School of Medicine, Madison, Wisconsin 53792

To assess the effect of polyamine blockade on urinary epithelium, growth of normal human urothelial cell cultures and human transitional cell carcinoma (TCC) cell lines in the presence of various inhibitors of polyamine synthesis was evaluated. All four human TCC cell lines tested were quite sensitive to the specific inhibitor of ornithine decarboxylase, -difluoromethylornithine (DFMO), requiring 1.0 mM DFMO to double generation time. Alternatively, all three human urothelial cultures tested required 5–20-fold higher DFMO concentrations to achieve similar growth inhibition. The inhibitory effect of DFMO on TCC was found to act synergistically with that of the inhibitor of S-adenosylmethionine decarboxylase, methylglyoxal bis(guanylhydrazone), and additively with that of recombinant ß-serine interferon. Addition of individual polyamines entirely prevented the inhibitory effects of DFMO and/or methylglyoxal bis(guanylhydrazone) but not that of ß-serine interferon. It appears that inhibition of polyamine synthesis and/or interconversion holds promise in the management of TCC and that the in vitro model described will be of value in investigating such clinical applications.

¹ Supported by Grants CA36908 (E. M. M.), CA44801 (E. M. M.), and CA29525 (C. A. R.) from the NIH.

² To whom requests for reprints should be addressed.

Received 5/ 5/87. Revised 10/13/87. Accepted 10/16/87.

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