DIFFERENTIAL ACTIVITY OF ASPIRIN, KETOPROFEN AND SULINDAC AS CANCER CHEMOPREVENTIVE AGENTS IN THE MOUSE URINARY-BLADDER

In vivo studies were conducted to compare the activity of three non-st eroidal anti-inflammatory drugs as inhibitors of urinary bladder carci nogenesis induced in B6D2F(1) (BDF) mice by N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN), Mice received continuous dietary exposure to non toxic doses of aspirin, sulindac or ketoprofen beginning 1 week prior to the first of eight weekly doses of 7.5 mg OH-BBN; studies were term inated at 24 weeks after the first carcinogen dose, Both dose levels o f sulindac (200 and 400 mg/kg diet) and both dose levels of ketoprofen (40 and 80 mg/kg diet) reduced the incidence of transitional cell car cinoma of the urinary bladder by >70% from that seen in dietary contro ls, The high dose of sulindac conferred the greatest protection agains t bladder cancer induction, In contrast, when administered at 400 and 800 mg/kg diet aspirin was inactive as a chemopreventive agent in the OH-BBN/BDF bladder cancer model, The significant potency of sulindac a nd ketoprofen as inhibitors of urinary bladder carcinogenesis, when co nsidered with their history of safe human use, suggests that these age nts merit further study as drugs for cancer chemoprevention in this ta rget tissue.