Biological effects of low-dose-rate irradiation of pancreatic carcinoma cells in vitro using 125I seeds.
OBJECTIVE
To determine the mechanism of the radiation-induced biological effects of 125I seeds on pancreatic carcinoma cells in vitro.


METHODS
SW1990 and PANC-1 pancreatic cancer cell lines were cultured in DMEM in a suitable environment. Gray's model of iodine-125 (125I) seed irradiation was used. In vitro, exponential phase SW1990, and PANC-1 cells were exposed to 0, 2, 4, 6, and 8 Gy using 125I radioactive seeds, with an initial dose rate of 12.13 cGy/h. A clonogenic survival experiment was performed to observe the ability of the cells to maintain their clonogenic capacity and to form colonies. Cell-cycle and apoptosis analyses were conducted to detect the apoptosis percentage in the SW1990 and PANC-1 cells. DNA synthesis was measured via a tritiated thymidine (3H-TdR) incorporation experiment. After continuous low-dose-rate irradiation with 125I radioactive seeds, the survival fractions at 2 Gy (SF2), percentage apoptosis, and cell cycle phases of the SW1990 and PANC-1 pancreatic cancer cell lines were calculated and compared.


RESULTS
The survival fractions of the PANC-1 and SW1990 cells irradiated with 125I seeds decreased exponentially as the dose increased. No significant difference in SF2 was observed between SW1990 and PANC-1 cells (0.766±0.063 vs 0.729±0.045, P<0.05). The 125I seeds induced a higher percentage of apoptosis than that observed in the control in both the SW1990 and PANC-1 cells. The rate of apoptosis increased with increasing radiation dosage. The percentage of apoptosis was slightly higher in the SW1990 cells than in the PANC-1 cells. Dose-dependent G2/M cell-cycle arrest was observed after 125I seed irradiation, with a peak value at 6 Gy. As the dose increased, the percentage of G2/M cell cycle arrest increased in both cell lines, whereas the rate of DNA incorporation decreased. In the 3H-TdR incorporation experiment, the dosimetry results of both the SW1990 and PANC-1 cells decreased as the radiation dose increased, with a minimum at 6 Gy. There were no significant differences in the dosimetry results of the two cell lines when they were exposed to the same dose of radiation.


CONCLUSIONS
The pancreatic cancer cell-killing effects induced by 125I radioactive seeds mainly occurred via apoptosis and G2/M cell cycle arrest.
Zhong-Min Wang, Jian Lu, Li-Yun Zhang, Zhi-Jin Chen, Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China.
Zhong-Min
ZM
Wang
Zhong-Min Wang, Jian Lu, Li-Yun Zhang, Zhi-Jin Chen, Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China.
Jian
J
Lu
Zhong-Min Wang, Jian Lu, Li-Yun Zhang, Zhi-Jin Chen, Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China.
Li-Yun
LY
Zhang
Zhong-Min Wang, Jian Lu, Li-Yun Zhang, Zhi-Jin Chen, Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China.
Xiao-Zhu
XZ
Lin
Zhong-Min Wang, Jian Lu, Li-Yun Zhang, Zhi-Jin Chen, Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China.
Ke-Min
KM
Chen
Zhong-Min Wang, Jian Lu, Li-Yun Zhang, Zhi-Jin Chen, Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China.
Zhi-Jin
ZJ
Chen
Zhong-Min Wang, Jian Lu, Li-Yun Zhang, Zhi-Jin Chen, Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China.
Fen-Ju
FJ
Liu
Zhong-Min Wang, Jian Lu, Li-Yun Zhang, Zhi-Jin Chen, Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China.
Fu-Hua
FH
Yan
Zhong-Min Wang, Jian Lu, Li-Yun Zhang, Zhi-Jin Chen, Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China.
Gao-Jun
GJ
Teng
Zhong-Min Wang, Jian Lu, Li-Yun Zhang, Zhi-Jin Chen, Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China.
Ai-Wu
AW
Mao
D017209:Apoptosis / Q000528:radiation effects; D001918:Brachytherapy / Q000379:methods*; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects; D006801:Humans; D007457:Iodine Radioisotopes; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*
D007457:Iodine Radioisotopes
125I radioactive seeds; Biological effects; PANC-1; Pancreatic cancer; SW1990