Biological Response of Chinese Hamster B14-150 Cells to Sequential Combined Exposure to Protons and 12C Ions.

Proton and ion radiation therapy, when used both as single radiation and in mixed radiation mode, have a number of advantages over the conventional γ-therapy that are determined by physical characteristics of accelerated particles. The paper presents the results of an in vitro study of the effectiveness of sequential exposures of Chinese hamster tumor cells B14-150 to proton (p) and 12C ion beams. We used 4 irradiation schemes differing by the sequence of exposure and the contribution of each radiation to the total dose. Synergism was shown for 12C ions dose contribution of 45% (taking into account the coefficient of relative biological efficiency) and the sequence 12C→p.

Post-Irradiation Recovery of B14-150 Fibrosarcoma Cells after Combined Irradiation with Low and High Linear Energy Transfer.

The use of radiation with low and high linear energy transfer (LET) in the same treatment regimen is promising in terms of increasing the efficiency and reducing the severity of radiation complications. Here we studied combined effect of protons (LET≈3 keV/µm) and heavy recoils (HR) induced by 14.5 MeV neutrons (LET≈290 keV/µm) on B14-150 fibrosarcoma cells. Comparison of the 4 irradiation schemes with different high-LET/low-LET dose ratios and the irradiation sequences revealed higher effectiveness of the combined action in the HR→protons sequence and with increasing HR dose contribution to 40% of the total dose. The observed effects were due to differences in the recovery of damages induced in cells by radiations with low and high LET.

Dose Field Shaping and Biological Effectiveness of the Effect of Pulsed Electron Accelerator Novac-11 on Mammalian Cells.

The development of technologies for using the Novac-11 pulsed electron accelerator in radiation therapy of animals with spontaneous neoplasms requires dosimetric and radiobiological studies. The studies were performed on cultured Chinese hamster V-79 fibroblasts after irradiation with 10 MeV electrons in a dose range up to 12 Gy and 60Co γ-radiation. Chemical dosimeters FBX and Fricke were used as additional test-systems. The depth dose curves were measured and the maximum dose depth of the electron beam was determined in tissue-equivalent phantoms. Cell survival and the data of chemical dosimetric systems showed that the effects of electron irradiation did not differ from that of 60Co γ-radiation. It was concluded that the use of Novac-11 in the therapy of animals with spontaneous neoplasms is advisable.

Evaluation of Antitumor Efficiency of High Intensity Radiation 169Yb Source on Experimental Sarcoma M-1.

Rats with sarcoma M-1 were exposed to high dose rate irradiation with 169Yb source. In 25 days after introduction of a trocar with sealed capsule with 169Yb source into the tumor, complete tumor regression was observed in 70% animals. The results suggest feasibility of using 169Yb source for high-dose rate brachytherapy and development of the personalized medicine approaches.

A comparative study of the biological effectiveness of 14-MeV neutron pulse and continuous radiation using mouse melanoma B-16 cells.

The study was carried out using compact neutron generators with a sealed tube operating in pulsed (neutron generator ING-031) and continuous (NG-14) modes. Neutron radiation was formed due to reaction T(d,n)(4)He. The average flow of 14-MeV neutrons was 6.6×10(9) ns(-1) for ING-031 and 1.2-1.6×10(10) n s(-1) for NG-14. Duration of an impulse was ∼1 ms and pulse frequency of 50 Hz. The gamma rays of (60)Со source with an average energy of 1.25 MeV were standard radiation. Biological efficacy was estimated using the clonogenic activity of mice melanoma B-16 cells. Comparison of biological effects of neutron irradiation in pulse and continuous modes showed no significant difference between them. RBE values of pulse (ING-031) and continuous (NG-14) neutron radiation were equal-in the range of 2.4-2.6. According to the clonogenic activity of melanoma B-16 cells no dose rate effect was observed within the studied range of neutrons doses and dose rates.

[The effectiveness of fractionated exposure of sarcoma M-1 to gamma-radiation and fast neutrons].

The effectiveness of fractionated exposure to gamma- and neutron radiation in their separate and combined use on the growth and functional morphology of mutant p53 sarcoma M-1 in rats was studied. Investigation techniques included immunostaining of PCNA and mutant p53 expressing cells, determination of mitotic activity and apoptotic death of tumor cells, as well as computer analysis of microscopic images. The antitumor efficacy of different types of radiation is shown to be determined by different levels of apoptosis induction, reduced proliferation and cellularity. Neutron radiation of the impulse generator has a marked damaging effect on the vasculature and the development of tumor necrosis. Fractionated irradiation at equal daily doses led to the decrease in the relative effectiveness of radio-inactivation of tumor cells. After 9 fractions of irradiation, the calculated value of the RBE of fast neutrons normalized to the input dose of 1 Gy by the coefficient of tumor growth inhibition, a reduced proliferative activity of PCNA and induced apoptosis of tumor cells was 3.4, 3.7 and 3.1, respectively. In the mode of daily superfractionation with splitting the dose in two fractions, the effectiveness of the combined exposure corresponded to the additive effect of gamma- and neutron radiation with a tendency toward synergism. There are reasons to believe that high resistance of sarcoma M-1 to the ionizing radiation impact is due not only to a fraction of hypoxic cells, but also the mutant status of p53 gene.

[Sensitivity of melanoma B16 side population to low- and high-LET radiation].

Cancer stem cells (CSC) found in multiple tumor types and cancer cell lines were shown to be more resistant to low-LET radiation in comparison to other cancer cells. Therefore, CSC are supposed to determine the long-term effect of cancer therapy. Research into the CSC sensitivity to high-LET radiation is of great interest because of the advances in hadron therapy. The aim of this investigation is to compare CSC and other cancer cell sensitivity to the low- (60Co gamma-rays) and high-LET (neutron) radiation. To identify CSC, we used the low cytometry-based side population (SP) technique based on the CSC capacity to produce the efflux of the vital dye Hoechst 33342. SP and non SP cells were sorted and exposed to gamma and neutron radiation at doses of 1-10 Gy and 0.1-4.7 Gy, correspondingly. We applied the colony-formation test to examine the SP and non SP survival rate after irradiation. It was shown that the sensitivity of SP to gamma-irradiation was lower than that of other cells: D0 average values (+/- SE) made up 2.3 +/- 0.3 Gy and 1.4 +/- 0.2 Gy, correspondingly (p = 0.047). The survival rate of SP and non SP did not differ after neutron irradiation. The values of relative biological effectiveness of neutron radiation relative to gamma-radiation at the D10 level were 2.6 for SP and 2.1 for other cells. The obtained results justify for the first time a high efficiency of application of neutrons in radiotherapy from the point of view of CSC elimination.

[The low dose and low dose rate cytogenetic effects induced by gamma-radiation in human blood lymphocytes in vitro. I. the results of physical and dosimetric study].

Physical and dosimetric characteristics of the gamma-radiation field which is formed in the room containing the 60Co radiation source were investigated on condition of an unclosed breech mechanism and the presence of the lead layer on the beam pathway. The inverse square law was approximately found for the dependence of the dose rate vs distance on the radiation source both for the unclosed breech mechanism and lead layer (4 and 9 cm wide) in the beam pathway. This finding indicated a non-significant contribution of the radiation scattered from the walls at the point of cytogenetic experiments. The Monte Carlo calculations showed that some changes in the efficient spectrum of gamma-radiation resulted in a decreased average energy of 60Co gamma-rays to 1.03, 1.17 and 1.07 MeV for the unclosed breech mechanism, behind 4 and 9 cm lead layers, respectively.