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1
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Co dała światu uparta polka, czyli od narodzin chemii radiacyjnej po współczesną biologię molekularną

100%
Szumiel I.
Kosmos
|
2011
|
vol. 60
|
issue 1-2
1-3
PL
Artykuł omawia pokrótce zasługi Marii Skłodowskiej-Curie dla nauk biologicznych. Przypomina, że przerabianie ton blendy smolistej w niezwykle prymitywnych warunkach doprowadziło do wyodrębnienia pierwszych pierwiastków radioaktywnych i zapoczątkowało powstanie chemii radiacyjnej. Wspomniany jest też mało znany osobisty udział Marii Skłodowskiej-Curie w czasie I wojny światowej w zorganizowaniu i prowadzeniu ruchomych punktów prześwietleń rannych żołnierzy. Odkrycie i badania pierwiastków radioaktywnych miało ważne konsekwencje dla nauk biologicznych XX wieku: umożliwiło zapoczątkowanie badań radiobiologicznych, radioterapię opartą na poznawaniu oddziaływań między promieniowaniem jonizującym i komórką na poziomie molekularnym oraz zastosowanie znaczników radioaktywnych, które przyczyniło się do powstania nowoczesnej biologii molekularnej.
EN
The paper briefly resumes the merits of Maria Skłodowska-Curie. It reminds the refining of several tons of pitchblende, to concentrate the radioactive components, the discovery of radioactive elements and emergence of radiation chemistry and also her initiative to use of mobile radiography units for the treatment of wounded soldiers during World War I. The main steps are listed in the development of radiation biology, radiotherapy based on understanding the interaction between ionising radiation and living cells at the molecular level and the use of radioactive markers that helped to establish the modern molecular biology.
2
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Chromatin acetylation, β-amyloid precursor protein and its binding partner FE65 in DNA double strand break repair

64%
Szumiel I., Foray N.
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2011
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vol. 58
|
issue 1
11-18
EN
Among post-translational modifications of chromatin proteins taking place in DNA double strand break (DSB) repair, acetylation plays a prominent role. This review lists several facts and hypotheses concerning this process. Lack of acetyltransferase TIP60 (HIV-Tat interacting protein of 60 kDa) activity results in cells with defective DSB repair. The enzyme is present in the nucleus in a multimeric protein complex. TIP60 dependent activation of ATM (ataxia telangiectasia mutated kinase) is an early event in the response to DNA breakage. Other important acetylations are those of histones H4 and γH2AX. Correct reconstruction of the damaged site is critical for survival and prevention of genetic and epigenetic changes in the cell that may affect the function of its daughter cells. Recently, two proteins with previously unsuspected functions in DSB repair have been identified as active in this process: Alzheimer β-amyloid precursor protein (APP) and its binding partner FE65, β-amyloid precursor binding protein. Their participation in DSB repair in both neuronal and non-neuronal cells is related to acetylation carried out by the acetyltransferase complex. The same function is ascribed to heterochromatin protein 1 (HP1). So far, the relations (if any) between TIP60 activation by HP1 and by the FE65 complex remain unidentified.
3
Content available remote

Elementy radiobiologii dla pilota Pirxa

51%
Deperas-Kamińska M., Szumiel I., Wójcik A.
Kosmos
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2006
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vol. 55
|
issue 4
337-345
EN
Contrary to the widespread opinion, interstellar space is not empty but filled with high energy particles that originate from within and from outside of our Solar system. these particles can induce ionization lesions in human cells and present a health hazard for astronauts. dna is the most sensitive component of the cell and induction of dna damage by ionizing radiation triggers a cascade of signals which can either push the cell towards committing suicide by apoptosis or initiate repair processes. a number of repair pathways exist but none of them is error-free. repair mistakes can lead to the formation of mutations which are potential sources of cancer. the actual doses received by the astronauts in space is a matter of debate. a number of studies have been performed to assess the dose by means of biological dosimetry. this method relies on the analysis of chromosomal aberrations in peripheral blood lymphocytes. most studies show an increased frequency of aberrations in lymphocytes of astronauts who spent at least several weeks in space. this clearly shows that space travel is associated with a risk of developing cancer.
4
Content available remote

Nonhomologous end-joining deficiency of L5178Y-S cells is not associated with mutation in the ABCDE autophosphorylation cluster

51%
Brzóska K., Kruszewski M., Szumiel I.
|
2006
|
vol. 53
|
issue 1
233-236
EN
Cells with mutated autophosphorylation sites in the ABCDE cluster of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are defective in the repair of ionising radiation-induced DSB, but show in an in vitro test the same DNA-PK activity as the cells possessing wild type enzyme. Nevertheless, the mutated DNA-PK is able to undergo ATP-dependent autophosphorylation and inactivation. This characteristics correspond well with the phenotypic features of the L5178Y-S (LY-S) cell line that is defective in DSB repair, shows a pronounced G1 phase radiosensitivity, but in which the level of DNA-PK activity present in total cell extracts is similar to that of its radioresistant counterpart L5178Y-R (LY-R) cell line. The purpose of this work was to examine the possible alterations in the sequence encoding the cluster of autophosphorylation sites in the DNA-dependent protein kinase in LY-S cells. Despite the presence of phenotypic features indicating the possibility of such alterations, no differences were found between the sequences coding for the autophosphorylation sites in L5178Y-R and L5178Y-S cells. In conclusion, the repair defect in LY-S cells is not related to the structure of the DNA-PK autophosphorylation sites (ABCDE casette).
5
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Repair of γ-ray-induced base damage in L5178Y sublines is damage type-dependent and unrelated to radiation sensitivity.

51%
Kruszewski M., Zastawny T. H., Szumiel I.
|
2001
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vol. 48
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issue 2
525-533
EN
The L5178Y (LY) murine lymphoma sublines LY-R and LY-S are differentially sensitive to ionizing radiation. The high radiation sensitivity of LY-S cells is related to impaired rejoining of DNA double strand breaks. We found previously that the γ-ray-induced base damage is higher in the more radiosensitive LY-S subline. Here, we examine the role of the repair of ionizing radiation induced base damage in relation to the radiosensitivity difference of these sublines. We used the GS/MS technique to estimate the repair rates of six types of base damage in γ-irradiated LY cells. All modified DNA bases identified in the course of this study were typical for irradiated chromatin. The total amount of initial base damage was higher in the radiation sensitive LY-S subline than in the radiation resistant LY-R subline. The repair rates of 5-OHMeUra, 5-OHCyt, 8-OHAde were similar in both cell lines, the repair rates of FapyAde and 8-OHGua were higher in the radiosensitive LY-S cell line, whereas the repair of 5-OHUra was faster in its radioresistant counterpart, the LY-R Altogether, the repair rates of the γ-ray-induced DNA base damage in LY sublines are related neither to the initial amounts of the damaged bases nor to the differential lethal or mutagenic effects of ionizing radiation in these sublines.
6
Content available remote

DNA damage induced by hydrogen peroxide treatment at 4°C and 37°C in murine lymphoma L5178Y sublines

51%
Kruszewski M., Szumiel I.
Acta Biochimica Polonica
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1994
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vol. 41
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issue 2
120-121
7
Content available remote

The response of L5178Y lymphoma sublines to oxidative stress: Antioxidant defence, iron content and nuclear translocation of the p65 subunit of NF-κB.

39%
Boużyk E., Grądzka I., Iwaneńko T., Kruszewski M., Sochanowicz B., Szumiel I.
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2000
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vol. 47
|
issue 4
881-888
EN
We examined the response to hydrogen peroxide of two L5178Y (LY) sublines which are inversely cross-sensitive to hydrogen peroxide and X-rays: LY-R cells are radioresistant and hydrogen peroxide-sensitive, whereas LY-S cells are radiosensitive and hydrogen peroxide-resistant. Higher initial DNA breaks and higher iron content (potentially active in the Fenton reaction) were found in the hydrogen peroxide sensitive LY-R cells than in the hydrogen peroxide resistant LY-S cells, whereas the antioxidant defence of LY-R cells was weaker. In particular, catalase activity is twofold higher in LY-S than in LY-R cells. The content of monobromobimane-reactive thiols is 54% higher in LY-S than in LY-R cells. In contrast, the activity of glutathione peroxidase (GPx) is about two times higher in LY-R than in LY-S cells; however, upon induction with selenium the activity increases 15.6-fold in LY-R cells and 50.3-fold in LY-S cells. Altogether, the sensitivity difference is related to the iron content, the amount of the initial DNA damage, as well as to the efficiency of the antioxidant defence system. Differential nuclear translocation of p65-NF-κB in LY sublines is due to the more efficient antioxidant defence in LY-S than in LY-R cells.
8
Content available remote

The rapid interphase chromosome assay (RICA) implementation: comparison with other PCC methods

39%
Sommer S., Buraczewska I., Sikorska K., Bartłomiejczyk T., Szumiel I., Kruszewski M.
|
|
issue 4
933-941
EN
A report is presented on the advantages of the rapid interphase chromosome assay (RICA) and the difficulties that may be met while implementing this method for application in biological dosimetry. The RICA test can be applied on unstimulated human lymphocytes; this is an advantage in comparison with the dicentric chromosomes or micronucleus tests. In the former two tests, stimulated lymphocytes are examined and hence, 48 h more are needed to obtain cells traversing the cell cycle. Due to the use of unstimulated nondividing cells, higher numbers of cells are available for RICA analysis than for dicentric chromosomes or micronuclei tests. Moreover, the method can be applied after exposure to ionizing radiation doses in excess of 5 Gy. Such doses cause a significant cell cycle delay or result in the loss of G2 phase and mitotic cells because of apoptosis. Therefore, the traditional biodosimetry based on the evaluation of the incidence of damage to chromosomes is very difficult to carry out. This is due to the lack of an adequate number of mitotic cells for analysis. RICA is free of this disadvantage. An automatic microscope can be used to retrieve cell images; automatic image analysis can also be used.
9
Content available remote

Sirtuin inhibition increases the rate of non-homologous end-joining of DNA double strand breaks

39%
Wojewódzka M., Kruszewski M., Buraczewska I., Xu W., Massuda E., Zhang J., Szumiel I.
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2007
|
vol. 54
|
issue 1
63-69
EN
Sirtuins (type III histone deacetylases) are an important member of a group of enzymes that modify chromatin conformation. We investigated the role of sirtuin inhibitor, GPI 19015, in double strand break (DSB) repair in CHO-K1 wt and xrs-6 mutant cells. The latter is defective in DNA-dependent protein kinase (DNA-PK)-mediated non-homologous end-joining (D-NHEJ). DSB were estimated by the neutral comet assay and histone γH2AX foci formation. We observed a weaker effect of GPI 19015 treatment on the repair kinetics in CHO wt cells than in xrs6. In the latter cells the increase in DNA repair rate was most pronounced in G1 phase and practically absent in S and G2 cell cycle phases. The decrease in the number of histone γH2AX foci was faster in xrs6 than in CHO-K1 cells. The altered repair rate did not affect survival of X-irradiated cells. Since in G1 xrs6 cells DNA-PK-dependent non-homologous end-joining, D-NHEJ, does not operate, these results indicate that inhibition of sirtuins modulates DNA-PK-independent (backup) non-homologous end-joining, B-NHEJ, to a greater extent than the other DSB repair system, D-NHEJ.
10
Content available remote

Cytotoxic and mutagenic effects of hydrogen peroxide in murine L5178Y sublines

38%
Kruszewski M., Szumiel I.
|
|
vol. 40
|
issue 1
42-45
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