We investigated whether exposure of rat brain to microwaves (MWs) of global system for mobile communication (GSM) induces DNA breaks, changes in chromatin conformation and in gene expression. An exposure installation was used based on a test mobile phone employing a GSM signal at 915 MHz, all standard modulations included, output power level in pulses 2 W, specific absorption rate (SAR) 0.4 mW/g. Rats were exposed or sham exposed to MWs during 2 h. After exposure, cell suspensions were prepared from brain samples, as well as from spleen and thymus. For analysis of gene expression patterns, total RNA was extracted from cerebellum. Changes in chromatin conformation, which are indicative of stress response and genotoxic effects, were measured by the method of anomalous viscosity time dependencies (AVTD). DNA double strand breaks (DSBs) were analyzed by pulsed-field gel electrophoresis (PFGE). Effects of MW exposure were observed on neither conformation of chromatin nor DNA DSBs. Gene expression profiles were obtained by Affymetrix U34 GeneChips representing 8800 rat genes and analyzed with the Affymetrix Microarray Suite (MAS) 5.0 software. In cerebellum from all exposed animals, 11 genes were upregulated in a range of 1.34-2.74 fold and one gene was downregulated 0.48-fold (P < .0025). The induced genes encode proteins with diverse functions including neurotransmitter regulation, blood-brain barrier (BBB), and melatonin production. The data shows that GSM MWs at 915 MHz did not induce PFGE-detectable DNA double stranded breaks or changes in chromatin conformation, but affected expression of genes in rat brain cells.
Single-fraction radiation therapy with 5 or 15 Gy (60)Co gamma radiation was combined with intraperitoneal injections of syngeneic interferon gamma (IFN-gamma)-transfected cells in rats with intracerebral N29 or N32 glioma tumors at days 7, 21 and 35 after inoculation. For intracerebral N29 tumors, single-fraction radiation therapy with 5 or 15 Gy had no significant effect on the survival time. Immunization with IFN-gamma-transfected N29 cells significantly increased the survival time by 61%. Single-fraction radiation therapy with 5 Gy combined with immunization increased the survival time significantly by 87% and complete remissions by 75% while with 15 Gy the survival time increased 45% with 38% complete remissions. For intracerebral N32 tumors, single-fraction radiation therapy with 15 Gy increased the survival time significantly by 20%. Immunization by itself had no significant effect with IFN-gamma-transfected N32 cells, but combined with 15 Gy single-fraction radiation therapy it increased survival time significantly by 40%, although there were no complete remissions. Based on these findings, we suggest a new therapeutic regimen for malignant glioma using single-fraction radiation therapy with a target absorbed dose of the order of 5-10 Gy combined with clinically verified immunotherapy.
The aim of the present study is to develop a mathematical model for evaluating therapeutic response of combined treatment modalities. The study was performed in rats of the Fischer-344 strain with rat glioma N32 or N29 tumors implanted subcutaneously on the thigh of the hind leg. Pulsed electric fields, PEF, with 16 exponentially decaying pulses with a maximum electric field strength of 140 V/mm and t 1/e = 1 ms were first applied to the tumors. Then within 5 min radiation therapy with 60 Co-gamma radiation, RT, was given in daily fractions of 5 Gy. The animals were arranged into one group of controls and 3 groups of different kind of treatments: PEF only, RT only or combination of PEF + RT. At about 4 weeks after inoculation, the tumors were given the treatment sessions during one week.In 2 experimental series with totally 52 rats with N32 tumors, of which 16 were controls, were given 4 sessions of PEF treatments and RT (totally 20 Gy). In a special experimental series with totally 56 rats with N32 tumors, of which 10 were controls, the different groups were given 1, 2, 3 or 4 treatment sessions respectively. Another strain of glioma tumor, N29 with 62 tumors of which 14 were controls was studied in 2 series given 4PEF + 4RT and 2PEF + 4RT respectively. This work demonstrate the use of our model for analyzing the combination PEF + RT, but it can also be used for evaluation the therapeutic effects of combining RT with chemotherapy or immunogene-therapy.
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