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Inhibition by Aspirin of N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide Initiation and Sodium Saccharin Promotion of Urinary Bladder Carcinogenesis in Male F344 Rats¹

Department of Pathology and Microbiology and the Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68105 [T. S., R. H., S. L. J., S. M. C.], and Veterans Administration Hospital, St. Louis, Missouri 63125 [T. V. Z.]

N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide (FANFT) is metabolically activated by several enzyme systems, including prostaglandin H synthase. Aspirin is an inhibitor of prostaglandin H synthase and has been shown to inhibit FANFT-induced bladder carcinogenesis when coadministered in the diet. To further evaluate the effects of aspirin on bladder carcinogenesis in the rat, we have coadministered aspirin with FANFT during the initiation phase and with sodium saccharin during the promotion phase of carcinogenesis. FANFT was administered in the diet at a level of 0.2% for 6 weeks as the initiator and sodium saccharin was administered in the diet at a level of 5% for 61 weeks as promoting stimulus. Aspirin was administered at a level of 0.5% with FANFT or with sodium saccharin, and appropriate control groups were included. Weanling male Fischer 344 rats were utilized and the chemicals were added to Agway Prolab 3000 rat chow. A 1-week interval was included between the FANFT and sodium saccharin administration during which the rats received either aspirin containing diet or control chow, depending on the treatment regimen of the group. Thirty rats were included in each group at the beginning of the experiment, except for the control group which contained 40. Rats given FANFT followed by saccharin had a bladder carcinoma incidence of 83%. Rats given aspirin with FANFT but not with saccharin had a carcinoma incidence of 20% and the rats fed aspirin with the saccharin but not with the FANFT had an incidence of 28%. FANFT followed by control diet resulted in a bladder carcinoma incidence of 10%, as was true for the rats given FANFT plus aspirin followed by control diet. However, the hyperplastic effects induced in the bladder epithelium by saccharin without prior FANFT administration were inhibited by coadministration with aspirin. These results indicate that aspirin inhibits both FANFT initiation and sodium saccharin promotion of bladder carcinogenesis, but the mechanisms involved would most probably be different for each.

¹ This research was supported in part by NIH Grants CA28015, CA32313, and CA36727.

² Present address: National Institute of Hygienic Science, Department of Pathology, Tokyo 158, Japan.

³ To whom requests for reprints should be addressed, at Department of Pathology and Microbiology, University of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, NE 68105.

Received 1/13/86. Revised 4/18/86. Accepted 5/ 2/86.

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