Papers by Marcin Kruszewski
Radiation and Environmental Biophysics, 2006
Activation of poly (ADP-ribose) polymerase -1 (PARP-1) is an early DNA damage response event that... more Activation of poly (ADP-ribose) polymerase -1 (PARP-1) is an early DNA damage response event that, together with phosphorylation of p53, prompts various cellular functions important in the maintenance of the genome stability. In mammalian cells, DSB are repaired by nonhomologous end-joining (NHEJ) and by homologous recombination (HR). To investigate the role of PARP-1 in HR, CHO-K1 wild type and xrs-6 mutant cell line were transfected with pLrec plasmids which carry two nonfunctional copies of the beta-galactosidase (lacZ) gene in a tandem array. In result of HR they can give rise to a functional copy of beta-galactosidase. To test whether PARP-1 affects the frequency of spontaneous and induced recombination repair, we treated CHO-K1 and xrs6 clones carrying chromosomally integrated pLrec with the PARP-1 inhibitor 3-aminobenzamide (3AB). Our results show that the spontaneous homologous intrachromosomal recombination frequency between the two lacZ copies was almost two orders of magnitude higher in xrs6 cells than in CHO-K1 cells, but that it was not affected by 3AB treatment. Induction of DNA damage by irradiation or electroporation of restriction enzymes did not significantly increase the recombination frequency. Furthermore, in both the cell lines, the effect of PARP-1 inhibition on DSB repair was examined using the neutral comet assay. There was no effect of 3AB treatment on DSB rejoining after 10 Gy irradiation. The results presented support the conclusion that PARP-1 is not directly involved in HR.
Toxicology, 2012
Serious concerns have been expressed about potential risks of engineered nanoparticles. Regulator... more Serious concerns have been expressed about potential risks of engineered nanoparticles. Regulatory health risk assessment of such particles has become mandatory for the safe use of nanomaterials in consumer products and medicines; including the potential effects on reproduction and fertility, are relevant for this risk evaluation. In this study, we examined effects of silver particles of nano-(20 nm) and submicron-(200 nm) size, and titanium dioxide nanoparticles (TiO 2 -NPs; 21 nm), with emphasis on reproductive cellular-and genotoxicity. Ntera2 (NT2, human testicular embryonic carcinoma cell line), and primary testicular cells from C57BL6 mice of wild type (WT) and 8-oxoguanine DNA glycosylase knock-out (KO, mOgg1 −/− ) genotype were exposed to the particles. The latter mimics the repair status of human testicular cells vs oxidative damage and is thus a suitable model for human male reproductive toxicity studies. The results suggest that silver nano-and submicron-particles (AgNPs) are more cytotoxic and cytostatic compared to TiO 2 -NPs, causing apoptosis, necrosis and decreased proliferation in a concentration-and time-dependent manner. The 200 nm AgNPs in particular appeared to cause a concentration-dependent increase in DNA-strand breaks in NT2 cells, whereas the latter response did not seem to occur with respect to oxidative purine base damage analysed with any of the particles tested.
European Journal of Heart Failure Supplements, 2008
Toxicology in Vitro, 2015
Titanium dioxide nanoparticles (TiO2 NPs) have found many practical applications in industry and ... more Titanium dioxide nanoparticles (TiO2 NPs) have found many practical applications in industry and daily life. A widespread application of TiO2 NPs rises the question about safety of their use in the context of potential occupational, environmental and intentional exposure of humans and biota. TiO2 NPs easily enter the body through inhalation, cross blood-brain barrier and accumulate in the brain, especially in the cortex and hippocampus. Toxicity of these NPs and the molecular mechanisms of their action have been studied extensively in recent years. Studies showed that TiO2 NPs exposure resulted in microglia activation, reactive oxygen species production, activation of signaling pathways involved in inflammation and cell death, both in vitro and in vivo. Consequently, such action led to neuroinflammation, further brain injury. A, spatial recognition memory and locomotor activity impairment has been also observed.
Acta biochimica Polonica, 2006
Cells with mutated autophosphorylation sites in the ABCDE cluster of DNA-dependent protein kinase... more 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...
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 2014
The incidence of ischemic heart disease (IHD) in patients with OSAS is estimated at around 20%. T... more The incidence of ischemic heart disease (IHD) in patients with OSAS is estimated at around 20%. This greatly affect a common risk factors for both diseases: male gender, obesity, age and diabetes and hypertension. Attention is drawn to the possibility of genetic determinants of IHD. The aim of study was to answer the question whether the presence of polymorphisms of selected genes possibly related to IHD may be useful to isolate the group of patients with OSAS, especially vulnerable as a complication of IHD. Materials and methods. The study included 600 people with OSAS, which was isolated in patients with IHD (127 people). The remaining 473 individuals were observed as a control group. The polymorphism of three genes were evaluated to find possible influence on the occurrence of IHD or myocardial infarction as follows: SREBF1 (sterol regulatory element binding transcription factor 1), REBF2 (sterol regulatory element binding transcription factor 2) and HIF1 (hypoxia inducible facto...
Pediatric endocrinology, diabetes, and metabolism, 2013
The role of diet in reduction of the risk of chronic diseases such as cardiovascular diseases, di... more The role of diet in reduction of the risk of chronic diseases such as cardiovascular diseases, diabetes mellitus, obesity, and metabolic syndrome has been widely documented. There is evidence that the link between diet and this kind of diseases is low grade chronic inflammation induced by some nutrients. Inflammation is a natural defense mechanism which helps to avoid tissue injuries caused by biological, physical and chemical factors. Adequate inflammatory process is defined by intensity and duration. As a chronic state (silent inflammation, low grade chronic inflammation), it became an etiologic factor of chronic diseases. References indicate that consumption of some nutrients ? such as fatty acids, glucose, bioactive plant compounds, some vitamins and minerals - is related with enhancement or alleviation of inflammatory state. Including them in diet could help to decrease the risk of chronic diseases and health complications caused by them. The aim of this paper is to show modula...
Particle and fibre toxicology, 2012
Respirable crystalline silica (silicon dioxide; SiO₂, quartz) particles are known to induce chron... more Respirable crystalline silica (silicon dioxide; SiO₂, quartz) particles are known to induce chronic inflammation and lung disease upon long-term inhalation, whereas non-crystalline (amorphous) SiO₂ particles in the submicrometre range are regarded as less harmful. Several reports have demonstrated that crystalline, but also non-crystalline silica particles induce IL-1β release from macrophages via the NALP3-inflammasome complex (caspase-1, ASC and NALP3) in the presence of lipopolysaccharide (LPS) from bacteria. Our aim was to study the potential of different non-crystalline SiO₂ particles from the nano- to submicro-sized range to activate IL-1β responses in LPS-primed RAW264.7 macrophages and primary rat lung macrophages. The role of the NALP3-inflammasome and up-stream mechanisms was further explored in RAW264.7 cells. In the present study, we have shown that 6 h exposure to non-crystalline SiO₂ particles in nano- (SiNPs, 5-20 nm, 50 nm) and submicro-sizes induced strong IL-1β res...
Pediatric endocrinology, diabetes, and metabolism, 2012
The results of food science investigations have confirmed the relationship between the type of ea... more The results of food science investigations have confirmed the relationship between the type of eaten food and health. Simultaneously, consumers are paying more and more attention to the kind of food they eat, as their awareness concerning the influence of proper food on health is increasing. On that base the conception of functional food has been created. This kind of food, besides being a source of essential macro- and micronutrients, exerts an additional positive influence on health. Probiotics and prebiotics containing products are a good example of functional food. These products provide not only essential nutrients but also microorganisms and polysaccharides, which are indigestible in the human alimentary tract, but exert a positive effect on human health. It may be a therapeutic or prophylactic effect due to specific affliction or may improve health in general. The paper - based on available literature - shows a positive influence of probiotics and prebiotics on human health, ...
Pediatric endocrinology, diabetes, and metabolism, 2011
Currently used dietary recommendations and requirements are generalized. It applies to both healt... more Currently used dietary recommendations and requirements are generalized. It applies to both healthy and ailing individuals. These recommendations are meant to avert leading chronic illnesses such as: type 2 diabetes mellitus, obesity, hyperlipidemia, cardiovascular diseases and hypertension. In the future it might be possible to give dietary advice tailored to every - sick and healthy - individual. Nutrigenomics and nutrigenetics are two fields derived from nutrition science and genetics. Their main goal is to elucidate the influence of interactions between genes and diet on individuals' health. This paper shows the examples of metabolic response changes according to diet and chosen gene polymorphisms. It will enable an effective prevention or management of chronic diseases by accurate diet and lifestyle matched to an individual's genetic makeup. It could be useful especially to define predisposition for type 2 diabetes mellitus in young children. It will be possible to chan...
Annals of agricultural and environmental medicine : AAEM, 2011
In recent years the attention of society, the media and politicians has focused on the negative p... more In recent years the attention of society, the media and politicians has focused on the negative phenomenon of the occurrence of an enormous amount of new psychoactive substances flooding the European market. In Poland and in Europe they are known under the name 'legal highs' or 'smart drugs'. In many countries these compounds present a serious social and health problem. The core of the problem is the fact that in the light of the law these substances are legal, while actually they imitate the eff ect of illegal narcotics. Smart drugs are sold allegedly as 'products not intended for human consumption', under the cover of 'collector's commodities', 'incense sticks' or 'bath salts'. Efforts undertaken by many countries, including Poland, are biased towards gaining control over this pathological phenomenon by placing the subsequent substances on the list of prohibited agents. However, the resilient chemical and pharmaceutical industry ...
Annals of agricultural and environmental medicine : AAEM, 2011
Human biomonitoring provides an efficient and cost-effective way to identify and quantify exposur... more Human biomonitoring provides an efficient and cost-effective way to identify and quantify exposure to chemical substances, including those having deleterious eff ects on human organisms. Once the risk of hazardous exposure has been identified and the mechanism of toxic eff ects has been elucidated, an ultimate decision about how to reduce exposure can be made. A particularly high risk of exposure to hazardous chemicals is associated with the use of pesticides in agriculture, especially the use of organophosphorous pesticides (OP), which are the most widely and commonly used insecticides worldwide. There is some strong evidence that chronic exposure to these compounds may have adverse eff ects on health. Exposure to pesticides has been associated with an increase in the incidence of non-Hodgkin's lymphoma, multiple myeloma, soft tissue sarcoma, lung sarcoma, and cancer of the pancreas, stomach, liver, bladder and gall bladder, Parkinson disease, Alzheimer disease, and reproductiv...
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Postepy biochemii, 2010
Formation of dinitrosyl iron complexes (DNICs), which can be described by general formula Fe(NO)2... more Formation of dinitrosyl iron complexes (DNICs), which can be described by general formula Fe(NO)2(L)2, where L is carbonyl-, nitrosyl- or imino- complexing ligand, was observed in many kinds of living organisms, in a wide spectrum of physiological conditions associated with inflammation, ischemia/reperfusion and cancer. Accumulation of DNICs coincides with intensified production of nitric oxide in macrophages, neurons, endothelial cells, Langerhans' cells and hepatocytes. Low-molecular thiol-containing DNICs (DNIC-(RS)2) show vasodilatory action and they are proposed to play a role of nitric oxide transducers and stabilizers. DNICs have been shown to modulate redox potential of the cell via inhibition of glutathione-dependent enzymes, such as glutathione reductase, S-transferase and peroxidase. Although there is a convincing experimental evidence for their NO and NO+ donating function, the nature of DNICs formed in biological systems, their stability and biological role is still...
Acta biochimica Polonica, 2006
Iron-sulfur clusters-containing proteins participate in many cellular processes, including crucia... more Iron-sulfur clusters-containing proteins participate in many cellular processes, including crucial biological events like DNA synthesis and processing of dioxygen. In most iron-sulfur proteins, the clusters function as electron-transfer groups in mediating one-electron redox processes and as such they are integral components of respiratory and photosynthetic electron transfer chains and numerous redox enzymes involved in carbon, oxygen, hydrogen, sulfur and nitrogen metabolism. Recently, novel regulatory and enzymatic functions of these proteins have emerged. Iron-sulfur cluster proteins participate in the control of gene expression, oxygen/nitrogen sensing, control of labile iron pool and DNA damage recognition and repair. Their role in cellular response to oxidative stress and as a source of free iron ions is also discussed.
Acta biochimica Polonica, 2000
We examined the response to hydrogen peroxide of two L5178Y (LY) sublines which are inversely cro... more 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 radio-resistant 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 co...
Environment pesticide effects principally depend on their niche distribution and chemical stabili... more Environment pesticide effects principally depend on their niche distribution and chemical stability/decomposition, according to seasonal variations. In areas of intensive pesticide use, populations are therefore more vulnerable to any detrimental effects, eg increased hypersensitivity, and may become conditioned to their short/long term actions depending on the patterns of use. Of particular concern are developmental disorders arising in children whenever the exposure is constant and of sufficient duration, even at low pesticide concentrations. A study investigated whether cytogenetic damage increased through prolonged pesticide exposure in n=117 children, aged 7-11 years, living in rural areas of intensive agriculture; controls being n=87 children from an agri-tourism region without pesticide exposure. DNA Single-Strand Breaks (SSB) were detected by the Comet assay in whole fresh blood samples together with 'formamidopyrimidine DNA-glycosylase (FPG)-sensitive sites' with th...
Annals of Agricultural and Environmental Medicine, 2014
Śliż K. Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility... more Śliż K. Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility to lung cancer in chronic obstructive pulmonary disease subjects. Ann Agric Environ Med. 2014, 21(3): 546-551.
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Papers by Marcin Kruszewski