Radiosensitivity of pancreatic carcinoma cell. In vitro and in vivo studies

MOHAMAD NORA; MEDINA VANINA; CROCI MAXIMO; CRESCENTI ERNESTO; NUÑEZ MARIEL; COCCA CLAUDIA; MARTIN GABRIELA; CRICCO GRACIELA; RIVERA ELENA; BERGOC ROSA

Octubre 25-30, 2004, Corfu , Grecia

Congreso; 7th International Conference of Anticancer Research; 2004

Radiosensitivity of pancreatic carcinoma cells. In vitro and in vivo studies. The objective of this paper was to determine, in vitro, the radiosensitivity of a human pancreatic cell line PANC-1 (derived from human pancreatic carcinoma), and the in vivo response of tumors to ionizing radiation when cells were inoculated in nude mice. Cells were seeded in RPMI medium (3500cells/flask) in triplicate and irradiated 24 hs later. The irradiation was performed using an IBL 437C H equipment calibrated with a TLD 700 dosimeter. The dose range was from 0 to 10 Gy and the number of colonies was scored on day 7 post-irradiation. Using adequate software, survival curves were plotted, fitted to the linear-quadratic model and the radiosensitivity parameters were determined. Results obtained were: alpha=0.53±0.09 Gy-1 and beta=0.18±0.03 Gy-2. When different drugs, such as insulin growth factor type-1 (IGF-1), were added to culture, the radiosensitivity parameters did not show significant difference. The in vivo effect of ionizing radiation was evaluated in tumors induced in nude mice by s.c. inoculation of PANC-1 cells. Three groups of mice were employed (n=5 each): A) one group received 2 ug/0.1 ml s.c. IGF-1 twice daily, over 4 days, before whole body irradiation with 10Gy; B) Another group of mice was irradiated as A without IGF-1 administration. The results indicate that IGF-1 treatment showed a clear protective effect on the small intestine and bone marrow: the number of intestinal crypts were significantly higher in A vs. B group and A group showed grade II aplasia vs. grade III in group B; C) another group of mice, bearing pancreatic tumors s.c.  developed by  inoculation of 3x10 6 PANC-1 cells, received local ionizing radiation. Radiation was delivered in 1.5 Gy/day fraction over 20days, using a Rich-Seifert X-ray generator, operating at 0.1 Gy/min. Dose rate was determined according to the OIEA TRS Nº: 277, 1987 Proceedings. The obtained results clearly showed a decreased tumor growth rate due to irradiation (p=0.0021). Molecular studies are under way at our laboratory to elucidate the mechanism of response to ionizing radiation in various types of malignant cells.