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EN
The aim of the study was to investigate the changes in proliferation rate, cell cycle and apoptosis of normal skin fibroblasts during fractionated irradiation with a fraction dose of 2 Gy. Fibroblasts were irradiated 5 days per week for 12 days using gamma irradiation. Twenty four hours after each fraction, and for three days after finishing experiment the cells were harvested, fixed, and BrdUrd labelling index (BrdUrdLI), cell cycle and level of apoptosis and debris were assessed. It was found that fractionated irradiation caused disturbances in the proliferation rate and the cell cycle. Irradiation caused also constant, statistically significant increase in the number of G2M cells and level of apoptosis and debris, which was observed even during 3 days after irradiation. Data indicate non equal biological effect of each fraction dose. Block at G2/M phase suggests accumulation of sublethal damage and increased radiosensitivity, which was manifested by elevated level of cell death (apoptosis and debris).
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nr 2
173-176
EN
Histone modifications are involved in the DNA damage response (DDR). Here, by utilizing an ELISA immunoassay we assessed the methylation at H3K9 (H3K9me2 and H3K9me3) in two cell lines with differential sensitivity to radiation-induced apoptosis, HeLa (sensitive) and MCF-7 (resistant). We found that DNA damage induction by γ-irradiation leads to considerable accumulation (up to 5-fold) of H3K9me2 and H3K9me3, but not of H4K20me3 (control modification) in MCF-7 cells (p<0.05). Interestingly, a lower dose (2 Gy) was more effective than 5 Gy. In HeLa cells a smaller effect (approx. 1.5-1.8-fold) was evident only at 5 Gy. In conclusion, our findings reveal that DNA damage leads to specific accumulation of H3K9me2 and H3K9me3 in a cell-type specific manner.
EN
The case of complete response of squamous cell oesophageal cancer to radiochemotherapy in patient previously operated due to hereditary retinoblastoma is presented. Second cancers in retinoblastoma survivors are the main cause of death in that group of patients in developed countries. There is little data on the outcome of treatment in those patients but the few papers available suggest rather poor prognosis. However, it is not clear whether the biology of cancer determined by RB gene mutation is responsible for that. The data suggesting decreased radio- and chemoresistance in cancers with decreased RB gene expression is discussed in the present paper. The role of that gene in the response to cancer treatment was showed in lung, breast and bladder cancer. Moreover, laboratory studies seem to confirm clinical observations and show that RB gene inhibition leads to increased cytotoxic effect of cisplatin, etoposide and 5-fluorouracil. It seems that without the incorporation of gene expression profiling into clinical practice further improvement in cancer treatment will be difficult to achieve.
EN
The aim of this study was to investigate the effect of signalling inhibition on survival and double-strand break (DSB) rejoining in cells differing in sensitivity to inhibitors, X-rays and bleomycin. Human glioma M059 cells, K (relatively radioresistant) and J (radiosensitive, defective in DSB rejoining for lack of DNA-dependent protein kinase catalytic subunit, DNA-PKcs) were pretreated with signalling inhibitors: tyrphostin AG 1478, specific for epidermalgrowth- factor-receptor (EGFR) kinase or PD 98059, specific for kinase MEK 1/2 (mitogen-activated, extracellular signal-activated kinases 1 and 2). Subsequently, the cells were X-irradiated or treated with bleomycin. Cell survival was determined by clonogenicity test. DSB rejoining was monitored with the use of pulsed-field gel electrophoresis (PFGE). We found that in X-irradiated M059 K cells EGFR kinase activity was necessary for efficient DSB rejoining and the kinase inhibitor, tyrphostin AG 1478, acted as radiosensitizer in the dose range that reduced cell survival to 0.7-0.8. Inhibition of EGFR kinase, however, did not decrease survival or affect DSB rejoining in DNA-PKcs-deficient M059 J cells. These results indicated that the decrease in cell survival was due to a disturbed DSB rejoining by the DNA-PK dependent system. In contrast, inhibition of MEK 1/2 kinase on EGFR downstream signalling pathway by PD 98059 did not affect DSB rejoining in either cell line and exerted a radioprotective effect.
PL
Międzynarodowa Komisja Ochrony Radiologicznej (ICRP) powołała do życia Grupę Roboczą (Task Group) nr 128 poświęconą możliwości indywidualizacji ochrony radiologicznej („Individualisation and Stratification in Radiological Protection: Implications and Areas of Application”). Przyczyną takiego działania jest między innymi fakt, iż wiele najnowszych badań naukowych potwierdziło, że każdy organizm w różny sposób reaguje na takie same dawki promieniowania jonizującego. Najwięcej danych na ten temat pochodzi od pacjentów onkologicznych, u których przed zastosowaniem radioterapii wykonywane są badania radiobiologiczne, mające na celu oszacowanie czy reakcja organizmu na promieniowanie nie będzie zbyt nasilona (tzw. promieniowrażliwość). W niniejszej pracy zaproponowano przykładową możliwość zindywidualizowania podejścia do ochrony radiologicznej, która z zasady nie uwzględnia takich czynników wpływających na odpowiedź na działanie promieniowania jonizującego, jak właśnie promieniowrażliwość. W artykule dokonano przeglądu metod radiobiologicznych, których potencjalne wykorzystanie do szacowania promieniowrażliwości zostało przetestowane w kilku wybranych pracach naukowych. Na tej podstawie zaproponowano własny uproszczony dwuparametryczny schemat badań, którego celem jest wyznaczenie poziomu promieniowrażliwości, mogący mieć potencjalne zastosowanie w ochronie radiologicznej pracowników narażonych na działanie promieniowania jonizującego.
EN
International Commission on Radiological Protection (ICRP) created a Task Group no. 128 on the possibility of individualization of radiation protection („Individualisation and Stratification in Radiological Protection: Implications and Areas of Application”). The reason for that is the fact, that many recent scientific studies showed, that each organism responses in different way for the same doses of ionizing radiation. Most of existing studies describe oncological patients which are radiobiologically tested before the radiotherapy, to assess their individual radiosensitivity (to prevent overreaction to radiation). In the presented paper we proposed exemplary approach to individualization of radiation protection, because today radiation protection does not implement the radiosensitivity phenomenon. This article contains the review of radiobiological methods from selected scientific studies which can be potentially used for radiosensitivity assessment. Based on that we proposed a simplified two parametric radiosensitivity test which can be potentially able to adapt for individual radiation protection of workers.
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