Objective  To study the effects of irradiation-induced wt-p53 positive feedback circuit on cell life cycle

apoptosis rate and irradiation sensitivity of adenocarcinoma of lung in vitro.   

Methods  The therapeutic group pE6R4-p53-EGFP/H1299 cells and the other 3 control groups H1299 (p53

-/-

)

pE6-p53-EGFP/H1299 and pR4-p53-EGFP/H1299 cells were irradiated with 8-Mev electron beam generated by a linear accelerator at a dose rate of 400 cGy/min and a sourceskin distance (SSD) of 100 cm

12 h exposure to irradiation. The cell life cycle and the rate of apoptosis were analyzed by FCM. Mean lethal dose (Do) and sensitive enhancement ratio (SER) index were calculated from the irradiation dosesurvival curve.   Results  In 12 h post 4-Gy 8MV-X-ray irradiation

FCM analysis showed that most cells in therapeutic group were arrested at G

0

/G

1

stage [(75.13±1.42)%

]

compared with the 3 control groups [(38.47±0.87)%

(62.57±0.76)% and (51.23±2.41)%

respectively

]

. After irradiation

the cell apoptotic rate in each group was higher than that in the cells without irradiation. The apoptotic rate in the therapeutic group was (23.73±0.21)%

which was 5.69

1.51 and 2.57 folds respectively higher in the 3 control groups[(4.17±0.12)%

(15.67±0.32)% and (9.23±0.15)%

]

. Do values were 0.91

1.073 and 1.413 Gy respectively in pE6R4-p53-EGFP/H1299

pE6-p53-EGFP/H1299 and H1299 cells. The SER

derived from Do values

was 2.63 and 1.34

respectively.    Conclusion  Irradiation up-regulates wt-p53 gene expression

regulates cell cycle and induces cell apoptosis. Thus this positive feedback circuit increases the sensitivity of lung adenocarcinoma to irradiation.