Early induction of mouse urinary bladder ornithine decarboxylase activity by rodent vesical carcinogens

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 or 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.