ObjectiveTo study the biological effects of nasopharyngeal carcinoma CNE-2 cells exposed with the the dose of 2 Gy in various partial fraction(PF) dose sequences so as to provide a new method and experimental basis to optimize the Intensity Modulation Radiated Therapy(IMRT) treatment plan in NPC.Methods3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and clonogenic assays were used to determine the radiation effects on cell proliferation and survival, respectively. The 2 Gy dose was divided into 2 or more PFs for delivery to simulate the delivery of clinical treatment fields. (1) Most irradiation sequences contained two parts consisting of at least 1 small PF, denoted by S which was 0.5 Gy or less, and a large PF,denoted by L which was 1 Gy or more; (2) the L-dose given either before or after the S-doses, adopting S-L/L-S series (2 fractions) and S-S-L/L-S-S series (3 fractions);and 3) delivery of all partial fractions within a fixed total time.ResultsSignificant differences in biologic effect were observed between sequences in which the L-dose was given before or after the S-doses in both the MTT and clonogenic assays.(1) In 2 and 3 fractionations, with the increase of S-dose, the survival fraction of S-S-L and S-L schemes declined gradually by clongenic assays. The smallest cell survival was seen when the S-dose was 40 cGy(S-L)or 50 cGy(S-S-L);(2)Nearly all the S-L and S-S-L schemes produced greater cytotoxic effects than that of the L-S and L-S-S schemes, the difference was significant (P<0.05) by t-test;(3)In a number of equal fractionation, the survival fraction of the group of S-dose (50 cGy, 40cGy, 20cGy) was significantly lower than that of the single irradiation (200 cGy), the difference was significant (P<0.05) by t-test,and there was no significant difference between the survival fraction of the group of L-dose (100 cGy) and single irradiation (200 cGy) (P <0.05). Conclusions1. CNE-2 cells may exist low-dose hyper-radiosensitivity in the dose range of≤0.5Gy.2. The biological effects of 2 Gy may differ in different clinical settings depending on the size and sequence of the partial fractions for nasopharyngeal carcinoma.The variation between cytotoxic effects is likely a result of the combination of low-dose hyper-radiosensitivity (HRS) and higher-dose increased radioresistance(IRR) effects.
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