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Early Induction of Mouse Urinary Bladder Ornithine Decarboxylase Activity by Rodent Vesical Carcinogens¹

Division of Clinical Oncology, Department of Human Oncology, Wisconsin Clinical Cancer Center, Madison, Wisconsin 53792

The responses of mouse urinary bladder ornithine decarboxylase (EC 4.1.1.17) and S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50) activities were studied following topical intravesical administration of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) or 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT), potent rodent bladder carcinogens. A single bladder topical application of ANFT or FANFT resulted in a significant increase over controls of ornithine decarboxylase activity within 5 hr, with a return to control levels by 10 hr. S-Adenosyl-L-methionine decarboxylase activity demonstrated a lesser response to topical ANFT or FANFT, achieving a level 2 to 3 times that of controls at 5 to 8 hr, followed by a gradual decline to control levels. Stimulation of activities of both enzymes was dose dependent over a range of 4.6 to 460 nmol of ANFT. ANFT-induced ornithine decarboxylase activity was principally localized in the bladder epithelium and was inhibited in a linear dose-response relationship by the synthetic retinoid, 13-cis-retinoic acid. Mice given FANFT p.o. demonstrated a significant increase over controls in ornithine decarboxylase activity within 12 hr, followed by a gradual decline to control levels by 72 hr.

¹ Supported in part by Grants CA 11946, CA 14520, and CA 14524 through the National Bladder Cancer Project and by Grant CA 20432. A preliminary report of this work has been made (23).

² To whom requests for reprints should be addressed, at Department of Human Oncology, Wisconsin Clinical Cancer Center, University of Wisconsin Center for Health Sciences, K4/528 CSC, 600 Highland Avenue, Madison, Wis. 53792.

Received 9/11/79. Accepted 3/11/80.