Wyniki wyszukiwania

1

Wpływ glimepyridu na parametry hemostazy u chorych na cukrzycę typu 2

100%

Sobol A. B., Drzewoski J.

Diagnostyka Laboratoryjna

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2006

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tom 42

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nr 4

2

Effect of gliclazide on nucleotide excision repair [NER] and non-homologous DNA end joining [NHEJ] in normal and cancer cells

81%

Sliwinska A., Sliwinski T., Kasznicki J., Drzewoski J.

Journal of Physiology and Pharmacology

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2010

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tom 61

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nr 3

347-353

The results of clinical studies revealed that gliclazide may reduce the risk of cancer in type 2 diabetic patients (T2DM), although the mechanism of possible protective effect is not sufficiently explored. The increased level of DNA damage and impaired DNA repair system in diabetes mellitus may play a substantial role in neoplastic transformation. Recently, we have demonstrated that gliclazide protected DNA against damage introduced by the oxidative stress, but its action on the DNA repair mechanisms is unclear. Therefore, the aim of this study was to assess whether gliclazide has any effect on the DNA repair pathways, e.g. nucleotide excision repair (NER) and non-homologous end joining (NHEJ). NER activity was assessed in the extract of human lymphocytes and pancreatic cancer cells (PANC-1) treated or not with gliclazide by use of an UV-irradiated plasmid as a substrate and by quantitative PCR performed to evaluate the efficacy of the removal of UV-induced lesions from the p53 gene by intact cells. The efficacy of NHEJ pathway was examined by a simple and rapid in vitro assay based on fluorescent detection of repair products. We did not observe significant differences between the efficiency of NER and NHEJ for extracts of lymphocytes alone and lymphocytes treated with gliclazide. Contrary, gliclazide increased the efficacy of NER (46.0% vs. 84.0%, p<0.01) and NHEJ (58.0% vs. 66.0%, p<0.05) in PANC-1 cells. In conclusion, the present study showed that gliclazide did not affect NER and NHEJ in human normal cells, but it may stimulate DNA repair in cancer cells.

3

Free radical scavengers can modulate the DNA-damaging action of alloxan

80%

Blasiak J., Sikora A., Czechowska A., Drzewoski J.

Acta Biochimica Polonica

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2003

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tom 50

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nr 1

Alloxan can generate diabetes in experimental animals and its action can be associated with the production of free radicals. It is therefore important to check how different substances often referred to as free radical scavengers may interact with alloxan, especially that some of these substance may show both pro- and antioxidant activities. Using the alkaline comet assay we showed that alloxan at concentrations 0.01-50 uM induced DNA damage in normal human lymphocytes in a dose-dependent manner. Treated cells were able to recover within a 120-min incubation. Vitamins C and E at 10 and 50 uM diminished the extent of DNA damage induced by 50 uM alloxan. Pre-treatment of the lymphocytes with a nitrone spin trap, a-(4-pyridil-1-oxide)- .-t-butylnitrone (POBN) or ebselen (2-phenyl-1,2-benzisoselenazol-3(2.H)-one), which mimics glutathione peroxides, reduced the alloxan-evoked DNA damage. The cells exposed to alloxan and treated with formamidopyrimidine-DNA glycosylase (Fpg) and 3-methyladenine-DNA glycosylase II (AlkA), enzymes recognizing oxidized and alkyl- ated bases, respectively, displayed greater extent of DNA damage than those not treated with these enzymes. The results confirmed that free radicals are involved in the formation of DNA lesions induced by alloxan. The results also suggest that alloxan can generate oxidized DNA bases with a preference for purines and contribute to their alkylation.

4

DNA damage in human colonic mucosa cells induced by bleomycin and the protective action of vitamin E

71%

Wozniak K., Arabski M., Malecka-Panas E., Drzewoski J., Blasiak J.

Cellular and Molecular Biology Letters

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2004

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tom 09

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nr 1

Using the alkaline comet assay, we showed that bleomycin at 0.1-5 μg/ml induced DNA strand breaks and/or alkali-labile sites, measurable as the comet tail moment, in human colonic mucosa cells. This DNA damage was completely repaired during a 120-minute post-treatment incubation of the cells. Post-treatment of the bleomycin-damaged DNA with 3-methyladenine-DNA glycosylase II (AlkA), an enzyme recognizing alkylated bases, gave rise to a significant increase in the extent of DNA damage, indicating that the drug could induce alkylative bases in DNA. We did not observe any change in the comet tail moment in the presence of catalase. Vitamin E ((+)-α-tocopherol) decreased DNA damage induced by bleomycin. The results obtained suggest that hydrogen peroxide might not be involved in the formation of DNA lesions induced by bleomycin in the colonic mucosa cells, and that vitamin E may exert protective effects on these cells.

5

Helicobacter pylori infection can modulate the susceptibility of gastric mucosa cells to MNNG

51%

Arabski M., Kazmierczak P., Wisniewska-Jarosinska M., Morawiec Z., Morawiec-Bajda A., Klupinska G., Drzewoski J., Chojnacki J., Blasiak J.

Cellular and Molecular Biology Letters

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2006

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tom 11

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nr 4

The pathogenesis of stomach cells can be associated with their susceptibility to exogenous dietary irritants, like nitrosamines such as dimethylnitrosamines (DMNA), and to the effects of non-dietary factors, including Helicobacter pylori infection. We used N-methyl-N'-nitro N-nitrosoguanidyne (MNNG) as a surrogate agent that induces a spectrum of DNA damage similar to DMNA. Using the alkaline comet assay, we showed that antioxidants--vitamins C and E, quercetin, and melatonin--reduced the genotoxic effect of MNNG in H. pylori-infected and non-infected human gastric mucosa cells (GMCs). To compare the sensitivity of the stomach and the blood, the experiment was also carried out in peripheral blood. We observed a higher level of DNA damage induced by MNNG in H. pylori-infected than in noninfected GMCs. We did not note any difference in the efficacy of the repair of the damage in either type of GMC. H. pylori infection may play an important role in the pathogenesis of GMCs, as it can modulate their susceptibility to dietary mutagens/carcinogens, thus contributing to gastric cancer.

6

A single nucleotide polymorphism in the 5'untranslated region of RAD51 in breast cancer

51%

Blasiak J., Przybylowska K., Czechowska A., Zadrozny M., Rykala J., Kolacinska A., Morawiec Z., Drzewoski J.

Cellular and Molecular Biology Letters

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2002

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tom 07

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nr Suppl.

7

Analysis of the G-C polymorphism in the 5'-untranslated region of the RAD51 gene in breast cancer

51%

Blasiak J., Przybylowska K., Czechowska A., Zadrozny M., Pertynski T., Rykala J., Kolacinska A., Morawiec Z., Drzewoski J.

Acta Biochimica Polonica

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2003

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tom 50

|

nr 1

The breast cancer suppressor proteins BRCA1 and BRCA2 interact with RAD51, a protein essential for maintaining genomic stability by playing a central role in homology-dependent recombinational repair of the DNA double-strand breaks. Therefore, genetic variability in the RAD51 gene may contribute to the appearance and/or progression of breast cancer. A single nucleotide polymorphism in the 5 - untranslated region of RAD51 (a G to C substitution at position 135, the G/C polymorphism) is reported to modulate breast cancer risk. We investigated the distribution of genotypes and frequency of alleles of the G/C polymorphism in breast cancer. Tumor tissues were obtained from postmenopausal women with node-negative and node-positive breast carcinoma with uniform tumor size. Blood samples from age matched healthy women served as control. The G/C polymorphism was determined by PCR-based MvaI restriction fragment length polymorphism. The distribution of the genotypes of the G/C polymorphism did not differ significantly (P > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no differences in the genotype distribution and allele frequencies between node-positive and node-negative patients. There were no significant differences between distributions of the genotypes in subgroups assigned to histological grades according to Scarf–Bloom–Richardson criteria and the distribution predicted by Hardy–Weinberg equilibrium (P > 0.05). Our study implies that the G/C polymorphism of the RAD51 gene may not be directly involved in the development and/or progression of breast cancer and so it may not be useful as an independent marker in this disease.

8

A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter in breast cancer

51%

Przybylowska K., Zielinska J., Zadrozny M., Rykala J., Kolacinska A., Morawiec Z., Drzewoski J., Blasiak J.

Cellular and Molecular Biology Letters

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2002

|

tom 07

|

nr Suppl.

Ograniczanie wyników

Wpływ glimepyridu na parametry hemostazy u chorych na cukrzycę typu 2

Effect of gliclazide on nucleotide excision repair [NER] and non-homologous DNA end joining [NHEJ] in normal and cancer cells

Free radical scavengers can modulate the DNA-damaging action of alloxan

DNA damage in human colonic mucosa cells induced by bleomycin and the protective action of vitamin E

Helicobacter pylori infection can modulate the susceptibility of gastric mucosa cells to MNNG

A single nucleotide polymorphism in the 5'untranslated region of RAD51 in breast cancer

Analysis of the G-C polymorphism in the 5'-untranslated region of the RAD51 gene in breast cancer

A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter in breast cancer