COMBINED EFFECT OF CHEMOPREVENTIVE AGENT N-(4-HYDROXYPBENYL) RETINAMIDE (4-HPR) AND GAMMA-RADIATION ON BLADDER-CANCER CELL-LINES

The incidence of bladder cancer has increased in the United States dur ing the past 50 years, consistent with increased exposure to bladder c arcinogens in the environment and tobacco use. Although N-(4-hydroxyph enyl) retinamide (4-HPR), a retinoid derivative, has been used as a ch emopreventive agent of bladder cancer in clinical trials, little is kn own about its mechanisms of action against bladder cancer cells. Previ ous studies suggest this chemopreventive agent may inhibit tumor growt h by inducing apoptosis. To further investigate this putative effect, we examined the effect of 4-HPR and gamma-radiation and their combined effects in three selected bladder cancer cell lines. Indeed, 4-HPR in duced apoptosis in these cell lines in a dose-dependent manner. A 2.5 mu M dose of 4-HPR and 50 rad of gamma-irradiation induced about 10% i ncrease in apoptotic cells, respectively. However, this low dose 4-HPR combined with low dose gamma-irradiation had a synergistic effect on apoptosis, in which apoptotic cells increased by more than 30%. The fi ndings have potential clinical implications and warrant further invest igations both in vitro and in vivo in bladder cancer.