2070

Backgrounds/Aims: Chemoradiation therapy with irradiation (IR) and a platinum agent, such as CDDP (Cisplatin) or CDGP (Nedaplatin), yields high cure rate in esophageal cancer. However, the mechanisms by which the platinum agent enhances the cellular susceptibility to IR has not been fully elucidated. When irradiation induces DNA double strand breaks (DSBs) in cells, histone H2AX is immediately phosphorylated. The phosphorylated H2AX is call as γH2AX, which is the sensitive marker of DSBs. Then, we studied the effect of platinum agent, such as CDGP, on the IR-induced γH2AX. Methods: Esophageal squamous cancer cells (JCRB0190 [KYSE-70]) were exposed to 0 or 2 Gy of IR. At 15 min before IR, CDGP or control medium was added to the medium (the final concentration of CDGP was 3 μM) and was removed by medium chaise at 3 hours after IR. Before and 1, 3, and 24 hours after IR, induction of γH2AX was determined by a immunofluorescence and westernblotting analyses. Tunnel staining was also performed. Results: 2 Gy of IR induced γH2AX, which reversed within 24 hours. This reversal was inhibited by incubation with 3 μM of CDGP for 3 hours. γH2AX induction by 3 μM of CDGP alone was weak. At 24 hours after IR, tunnel positive cells were observed in cells treated with IR and CDGP. When cells were treated with 2 Gy of IR alone or 3 μM of CDGP 3 hours alone, tunnel positive cells were very small throughout the study period (0 - 24hrs). Conclusion: The low dose of CDGP inhibits the repair of DSBs induced by IR, which would be related to the high cure rates of chemoradiation therapy for esophageal cancer with IR and CDGP.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]