Bax is an important determinant for radiation sensitivity in esophageal carcinoma cells.
Apoptosis is a crucial phenomenon for radiation-induced cell death. Since Bax plays a critical role in inducing apoptosis via p53-dependent and -independent pathways, we analyzed a role of Bax in radiation sensitivity in esophageal carcinoma cells. Using eight human esophageal carcinoma cell lines, irradiation was performed with cobalt-60 (60Co) gamma-rays. Radiation sensitivity was determined by induction of apoptosis, which was assessed by morphological change in nuclear condensation of chromatin, DNA ladder formation and apoptosis-related genes after irradiation. The survival curve was evaluated by clonogenic assay using a parameter D0 after irradiation, compared to that of the control. After transfection of the bax gene into low radiation sensitivity, TE-1 cells were conducted by lipofection method using pSFFV-Neo vector carrying bax cDNA. Radiation sensitivity of esophageal carcinoma cells was associated with induction of apoptosis, in a time- and dose-dependent manner. Induction of apoptosis affects early responsiveness to irradiation rather than the parameter D0. Radiation-induced apoptosis was associated with an increase in expression of bax gene, regardless of p53 genetic status. The introduction of the bax gene into a low radiation sensitivity cell line, TE-1, enhanced radiation sensitivity in association with increased apoptotic cell death after irradiation. Radiation sensitivity of esophageal carcinoma cells can be evaluated by induction of apoptosis, as an early predictive marker for radiation response. The proapoptotic gene bax plays a critical role in the determination of tumor response in radiation therapy.
Kim
Ryungsa
R
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. rkim@hiroshima-u.ac.jp
Inoue
Hideki
H
Toge
Tetsuya
T
D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein