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Toxicologic Pathology
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Journal Article

The Heterotopically Transplanted Rat Urinary Bladder as a Model for Detection of Tumor-Promoting Urinary Growth Factor(s)

Ryoichi Oyasu

Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611

Seishi Konno

Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611

Julie Stevens

Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611

Osamu Hayashi

Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611

The heterotopically transplanted rat urinary bladder (HTB) was developed in our laboratory as a model to study the role of urine in urinary bladder carcinogenesis. With this model, normal urine was found to enhance urinary bladder carcinogenesis initiated by N-methyl-N-nitrosourea or N-butyl-N-(4-hydroxybutyl)nitrosamine. Two crude urinary components (Fractions I and II) were obtained by gel filtration chromatography; they stimulated ornithine decarboxylase (ODC) in a test bladder carcinoma cell line 804G, and promoted carcinogenesis in the HTB system. Fraction I was found to stimulate growth of 804G cells in vitro. Preliminary data indicate that Fraction I contains at least one, and possibly two heat-stable ODC-inducible and mitogenic components. Further characterization of these components is in progress. The HTB system has been demonstrated to be useful for other investigations; for example, {alpha}-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ODC, when instilled repeatedly to the bladder lumen, inhibited tumorigenesis in HTBs.

Toxicologic Pathology, Vol. 14, No. 3, 331-334 (1986)
DOI: 10.1177/019262338601400307
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