Abstract
Interferons (IFNs) have established activities as antivirals and inhibitors of viral and transplantable tumors. To establish whether IFNs or their inducers can affect induction of carcinogenesis in vivo, the bladder-specific carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) was administered in the diet at 0.11 or 0.13% (w/w) to female C3H/He mice beginning at 7 weeks of age. Mice treated with the IFN-inducing bropirimine [2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone] i.p. twice a week for 14 weeks starting on day 30 of start of FANFT feeding developed fewer transitional cell carcinomas (TCC) than mice treated with the vehicle. Bropirimine (200 mg/kg twice a week) orally resulted in even greater effectiveness: 6 of 43 bladders with TCC for bropirimine-treated mice versus 24 of 39 for control glycine buffer-treated mice (P < 0.01, χ2 test). Mice treated i.p. daily on days 29 through 210 with 5,000 units of β interferon (specific activity, 2.0 × 108 units/mg) had 0 of 15 TCC while control mice had 7 of 13 TCC (P < 0.001). Bladders of untreated mice were also significantly heavier than those of β interferon- or bropirimine-treated mice. This dose of IFN treatment was confirmed as effective in a second experiment, in which mice were treated daily on days 30–223 with 5,000 units α/β interferon (specific activity, 1.2 × 107 units/mg). This resulted in 4 of 25 bladders with TCC versus 24 of 39 for control mice (P < 0.001). A higher dose of IFN (50,000 units α/β interferon daily) was toxic; 24 of 30 mice died within 2 months. IFN and an IFN inducer, bropirimine, inhibited development and progression of FANFT-induced bladder TCC in vivo and thus may have roles as chemopreventive modalities.
Supported in part by grants from NIH (CA-20432), the American Cancer Society, the Upjohn Company, and Triton Biosciences. E. C. B. is an American Cancer Society Professor of Clinical Oncology.
