Inhibition of cellular growth of melanoma cell lines by heterogeneous beta chronic irradiation at very low dose rate

MICHELIN S.; GALLEGOS C.E.; DUBNER D.; CRUZATE J.; FAVIER B.; CAROSELLA E. D.

Workshop; Third International MELODI Workshop; 2011

Introduction: Radioisotopes that decay via beta emission are widely used in science and medicine. The main advantage of beta-emitters is the relatively long path length in biological tissue (in the mm range), The objective of this work was to determine the inhibition of cellular growth of melanoma cells (melanoma cells are one of the most radioresistant tumor cells) by beta irradiation at very low dose rate using a simple and economic device. We compare it with the high dose rate gamma irradiation. Materials and methods: Cell culture: Human melanoma cell lines, FON and M8 were used. The cells were seeded 1 day before the start of the irradiation on 25 cm2 tissue culture flasks and the final cell number was determined at the end of irradiation period (4 to 6 days) Beta irradiation system: The system is composed of two identical tissue culture flasks superposed. The bottom flask (irradiation flask) was loaded by adding 32P orthophosphate solution. The absorbed dose in the upper culture flask and the isodose curves were calculated applying MCNPX 2.5f Monte Carlo code coupled to photon and electron cross sections from ENDF/B-VI library and validated by Gafchromic EBT2 film dosimetry. The irradiation and cell culture system was kept in incubator at 37°C and with 5% CO2 until the total dose was delivered. The final dose was 2 Gy and the initial dose rate was 12-15 mGy/h. The dose ranged from 100% in the center of the flask, to 67% at the external limit. Gamma irradiation: Both cells line were irradiated with 2 Gy at 30.000 mGy/h with Gammacell 220 at room temperature and 6 days post irradiation the number of viable cells was determined. Results The diminution for the survival of FON and M8 melanoma cells respect to the control by beta irradiation was 28,61±7,6 % and 40,75±5,8% and for gamma irradiation was 28,33±9,5% and 45,22±7 % respectively Discusion We determine the effectiveness in producing un significant cell death of two melanoma cell lines at very low dose rate beta irradiation (12-15 mGy/h) and we compare this effect with high dose rate gamma irradiation (30.000 mGy/h). This last dose rate is in the range of the dose rate used in radiotherapy. Gamma irradiation was employed because the relative biological efficiency is similar to beta irradiation For FON and M8 cell lines, cell survival diminution respect to controls was significant and independent of the dose rate. Studies are in progress to determine if the mechanisms that influence cell killing for low and high dose rate are different and if the bystander effect is involved in this response at very low dose rate. This irradiation system, which represent a similar radiodiagnostic, radioimmunotheraphy and brachytherapy situation because there is a continuous emission of exponentially decreasing low-dose-rate irradiation with heterogeneous dose deposition, permitted us to study in very simple and economic mode, different dose rate only changing the activity of beta emitter.