The Role Of DNA Damage Repair In The Apoptosis Induced By 4HPR In Bladder Cancer Cell T24

N- [4-hydroxyphenyl] retinamide (4HPR), a synthetic derivative of ATRA, was reported efficacy as chemopreventive agent for breast, prostate and bladder cancer in some clinical trails and shown to inhibit carcinogenesis in animal models for some cancers . The modification of the carbosyl end of retinoic acid with a N-4-hydroxyphenyl group resulted in the formation of a compound with increased effectiveness as chemopreventive agent as well as reduced toxicity compared to other retinoids. 4HPR has been shown to modulate a wide variety of cellular processes, including proliferation, differentiation, and apoptosis. Because of its structure similarity to retinoids, 4HPR has been thought to act through classical retinoids receptor system. Transactivition studies haveshown that 4HPR can activate retinoic acid receptor(RAR) α, β and retinoid X receptor (RXR). RAR α / β antagonists supperss 4HPR-induced apoptosis. There are also data supporting effects of 4HPR which is independent of retinoid receptor activation. It suggest that the mechanisms of apoptosis induced by 4HPR are complex and probably act through the RAR-dependent and -independent pathway. Recent reports suggest that 4HPR induced-apoptosis mediated through in increase in free radicals, reactive oxygen species, ceramide levels, NO and caspase-3 activity.Bladder cancer is most common urinary system tumor and the second most common tumor in European and American males, with an estimated 336,000 new cases diagnosed in 2000 worldwide. Nearly 90% of all primary bladder tumors are transitional cell carcinoma (TCC). Approximately 70% of TCC cases are superficial, low grade and noninvasive papillary tumors. However, of these cases as many as 80% will recur. Because of the role in urothelial differentiation, in recent years retinoids have entered the field of the therapy of bladder. 4HPR is one of the chemical compounds with chemotherapeutic activity formed by the modification of retinoids.In this study we would like to know the role of DNA damage and repair in the apoptosis induced by 4HPR in bladder cancer cell T24. 1. The apoptosis induced by 4HPR in T24 cells4HPR induced a time-and dose-dependent decrease in the rate of survival of T24 cells. A dose-dependent increase in the percentage of apoptosis cells was detectable at 1.8%, 4.0% and 10.5%, respectively in 2.5, 5.0, and 10.0 umol/L 4HPR treated cells at 6 day.In this study, a dose dependent increase in the intracellular reactive oxygen species level was observed in T24 cells treated with 2.5, 5.0, and 10.0 umol/L 4HPR for 1hr and in 1.5, 2 and 3-fold increased intensity, respectively. We also found antioxidant...