ABROGATION OF THE G2/M ARREST ENHANCED THE CYTOTOXIC EFFECTS BY CARBON-ION BEAMS

The aim of this study is to clarify cell cycle distribution and cytotoxicity after carbon-ion beams (C-ions). One human malignant melanoma cell line, HMV-I was exposed to X-rays or 290 MeV/u C-ions at the center of SOBP. We applied flow cytometry technique and colony formation assay. C-ions induced G2/M arrest effectively more than X-rays at 24 h. The iso-effect dose, i.e. the 10% survival dose (5.0Gy for X-rays, 2.7Gy for C-ions) was used to examine the cell cycle kinetics. G2/M fraction increased immediately after irradiations, and showed a peak at 15 h. G2/M arrest cells were stayed long time after C-ions, whereas it released quickly after X-rays. In addition, the mRNA expression of molecules related with the arrest was suppressed with D10 dose and the effects were transitory after X-rays, whereas C-ions showed prolonged suppression. The arrest was released significantly by caffeine, and the cell killing by C-ions was enhanced with caffeine together. It is suggested that the release from G2/M arrest after C-ions can enhance the cytotoxic effects. Repair of complex DNA damage by C-ions takes long time. When it released intermediate of the process, incomplete repaired damage cause cell death.
MICROS 2009 15th International Symposium on Microdosimetry