Jolanta Gromadzińska

Publications of Jolanta Gromadzińska

• 4-Week inhalation toxicity of 2-methylnaphthalene in experimental animals.

  Authors: Radosław Swiercz, Wojciech Wąsowicz, Jan Stetkiewicz, Jolanta Gromadzińska, Wanda Majcherek

  International journal of occupational medicine and environmental health. 12/2011; 24(4):399-408.

  This paper presents toxic effects of 2-MN in laboratory animals under conditions of 4-week inhalation exposure to 2-methylnaphthalene (2-MN) vapors. Male Wistar rats were exposed to 2-MN vapors at aThis paper presents toxic effects of 2-MN in laboratory animals under conditions of 4-week inhalation exposure to 2-methylnaphthalene (2-MN) vapors. Male Wistar rats were exposed to 2-MN vapors at a nominal concentration of 0, 2, 10 or 50 mg/m(3) in dynamic inhalation chambers for 4 weeks (6 h/day, 5 days/week). After 4 weeks of inhalation exposure the animals were necropsied. Blood samples were collected and selected organs were weighted and prepared for histological examinations. The effects of the increased levels of exposure to 2-MN experienced by the experimental rats were as follows: a) increasing γ-glutamylotransferase activity, b) stimulation of the hematopoietic system, c) lower cholesterol concentrations, d) higher number of goblet cells in lobar bronchi, e) hyperplasia of hepatic bile ducts. Four-week exposure of the animals to 2-MN at 2 mg/m(3) proved to be the no-observed-adverse-effect-level (NOAEL), while 10 mg/m(3) appeared to represent the lowest-observed-adverse-effect-level (LOAEL).

• GSTP1 mRNA expression in human circulating blood leukocytes is associated with GSTP1 genetic polymorphism.

  Authors: Edyta Reszka, Zbigniew Jabłonowski, Edyta Wieczorek, Jolanta Gromadzińska, Marek Sosnowski, Wojciech Wąsowicz

  Clinical biochemistry. 06/2011; 44(13):1153-5.

  We explored association between GSTP1 Ile(105)Val (rs1695) polymorphism and GSTP1 mRNA expression in circulating blood leukocytes. GSTP1 transcripts level and polymorphism were determined byWe explored association between GSTP1 Ile(105)Val (rs1695) polymorphism and GSTP1 mRNA expression in circulating blood leukocytes. GSTP1 transcripts level and polymorphism were determined by Real-Time PCR in 51 bladder cancer and 90 healthy men. Individuals with at least one GSTP1 Val(105) variant allele possessed higher GSTP1 mRNA level in blood leukocytes compared to GSTP1 Ile(105)Ile carriers. GSTP1 Ile(105)Val gene polymorphism influences its expression in blood, regardless of cancer disease.

• Hypermethylation of p16 and DAPK promoter gene regions in patients with non-invasive urinary bladder cancer.

  Authors: Zbigniew Jabłonowski, Edyta Reszka, Jolanta Gromadzińska, Wojciech Wąsowicz, Marek Sosnowski

  Archives of medical science : AMS. 06/2011; 7(3):512-6.

  The aim of the study was to examine the frequency of methylation status in promoter regions of p16 and DAPK genes in patients with non-invasive bladder cancer. Forty-two patients (92.9% men, 73.8%The aim of the study was to examine the frequency of methylation status in promoter regions of p16 and DAPK genes in patients with non-invasive bladder cancer. Forty-two patients (92.9% men, 73.8% smokers, 71.4% T1G1, 19.1% T1G2, 9.5% T1G3) and 36 healthy controls were studied. Isolation of genomic DNA from blood serum and methylation-specific PCR (MSP) were applied. Methylation status - methylated and unmethylated promoter regions of p16 and DAPK genes were analysed. Seventeen out of 42 patients (40.5%) had the methylated p16 gene, while methylation of the DAPK gene was seen in 27 of 42 cases (64.3%). In 12 patients (28.6%) both analysed genes were methylated. A statistically significant (p = 0.046) higher frequency of DAPK gene methylation (71.4%) was observed in patients with lower grade (G1) bladder cancer. Detection of the aberrant hypermethylation of DAPK and p16 genes in blood DNA from non-invasive bladder cancer patients might offer an effective means for earlier auxiliary diagnosis of the malignancy.

• Polish mother and child cohort study--defining the problem, the aim of the study and methodological assumption.

  Authors: Kinga Polańska, Wojciech Hanke, Jolanta Gromadzińska, Danuta Ligocka, Ewa Gulczyńska, Wojciech Sobala, Wojciech Wásowicz

  International journal of occupational medicine and environmental health. 01/2009; 22(4):383-91.

  Exposures during prenatal period have implications for pregnancy outcome as well as for children's health, morbidity and mortality. Prospective cohort study design allows for the identification ofExposures during prenatal period have implications for pregnancy outcome as well as for children's health, morbidity and mortality. Prospective cohort study design allows for the identification of exposures that may influence pregnancy outcome and children's health, verification of such exposures by biomarker measurements and notification of any changes in exposure level. Polish Mother and Child Cohort Study (REPRO_PL) is multicenter prospective cohort study conducted in 8 different regions of Poland. The final cohort is intended to comprise 1300 mother-child pairs to be recruited within 4-year period (2007-2011). The recruitment and all scheduled visits are conducted in maternity units or clinics in the districts included in the study. The women are followed-up 3 times in pregnancy (once in each trimester) and after delivery for the notification of pregnancy outcome. During each visit, detailed questionnaire and biological samples are collected including saliva, urine, hair, maternal blood and cord blood. About 6 weeks postpartum, breast milk from part of the women is collected. The study concentrates on the identification and evaluation of the effects of prenatal environmental exposure on pregnancy outcome and children's health. Specific research hypotheses refer to the role of heavy metals, exposure to polycyclic aromatic hydrocarbons (PAHs) and environmental tobacco smoke (ETS) in the aetiology of small-for-gestational-age (SGA) and preterm delivery (PD). The role of oxidative stress putative mechanism and pregnant women nutritional status will be investigated. Based on questionnaire data, the impact of occupational exposures and stressful situations will be evaluated. The results of the study will become available within the next few years and will help to determine levels of child prenatal exposure in several areas of Poland and its impact on course and outcome of pregnancy.

• Selenium and cancer: biomarkers of selenium status and molecular action of selenium supplements.

  Authors: Jolanta Gromadzińska, Edyta Reszka, Katharina Bruzelius, Wojciech Wasowicz, Björn Akesson

  European journal of nutrition. 06/2008; 47 Suppl 2:29-50.

  BACKGROUND: The relationship between selenium and cancer involves many different aspects. These include the forms of selenium present in the diet and in the body, their functions and mechanisms ofBACKGROUND: The relationship between selenium and cancer involves many different aspects. These include the forms of selenium present in the diet and in the body, their functions and mechanisms of action, and methods employed in assessing an individual's selenium nutritional status-both in general, and in epidemiological studies of the risk of cancer in relation to diet, as well as in connection with long-term trials for investigating the disease-preventive potential of selenium supplementation. AIM OF THE REVIEW: To review different aspects on selenium metabolism, the occurrence of different selenoproteins and their use as biomarkers of selenium status, the results of intervention trials of the cancer-preventive effects of selenium supplementation, the mechanisms of action involved, together with epidemiological findings on relations between the selenium status in the body and risk of cancer. RESULTS AND CONCLUSIONS: The rapid advance in the knowledge of different selenoproteins and their biological functions has opened up new possibilities for the understanding of the biological effects of selenium supplementation. A wide variety of effects of different forms and doses of selenium has been observed in a number of experimental systems, and it is at present difficult to pinpoint the mechanism that may explain the positive preventive effects of selenium supplementation observed in some human long-term trials. Moreover, additional such trials are needed to define the benefits and risks of different types and doses of selenium supplements which in the future may be implemented for public health reasons. Another necessary focus for future research is a better understanding of the mechanisms by which selenium interferes with the carcinogenesis process.

• Genotoxic effects in C57Bl/6J mice chronically exposed to arsenate in drinking water and modulation of the effects by low-selenium diet.

  Authors: Jadwiga Palus, Dobrosława Lewińska, Elzbieta Dziubałtowska, Wojciech Wasowicz, Jolanta Gromadzińska, Konrad Rydzyński, Małgorzata Stańczyk, Joanna Arkusz, Małgorzata Trzcinka-Ochocka, Maciej Stepnik

  Journal of toxicology and environmental health. Part A. 11/2006; 69(20):1843-60.

  In C57Bl/6J mice chronically exposed to arsenate in drinking water at 50, 200, or 500 microg As/L, genotoxic effects in bone-marrow cells using micronucleus test and in peripheral blood leukocytesIn C57Bl/6J mice chronically exposed to arsenate in drinking water at 50, 200, or 500 microg As/L, genotoxic effects in bone-marrow cells using micronucleus test and in peripheral blood leukocytes using the comet assay were determined after 3, 6 or 12 mo. To assess the modulating role of selenium in development of the effects, the animals were fed a specially prepared low-selenium diet and were supplemented with sodium selenite (200 microg Se/L) in drinking water (supplemented groups) or were without Se supplementation (nonsupplemented groups). Measurements of glutathione peroxidase activity in erythrocytes and plasma as well as selenium concentration in plasma were performed after 3, 6, and 12 mo and showed a marked decrease in values in animals in non-Se supplemented compared to Se-supplemented groups. After 3 mo of arsenic exposure in the Se-supplemented animals the level of DNA fragmentation (without Endo III and Fpg enzymes) did not differ from the control; however, increased oxidative damage of purine and pyrimidine bases was observed. In groups not supplemented with Se, an increase of DNA fragmentation was observed; however, the levels of oxidative DNA damage in these groups did not differ from the control. None of the positive effects observed in the comet assay after 3 mo was related to arsenate concentration. The levels of DNA damage after 6 and 12 mo of exposure to arsenic as well as the frequency of micronuclei after 3, 6, and 12 mo did not differ significantly between exposed and control animals, irrespective of Se supplementation status.

• Red blood cell and plasma glutathione peroxidase activities and selenium concentration in patients with chronic kidney disease: a review.

  Authors: Bronisław A Zachara, Jolanta Gromadzińska, Wojciech Wasowicz, Zbigniew Zbróg

  Acta biochimica Polonica. 02/2006; 53(4):663-77.

  The metabolism of oxygen in aerobic organisms leads to generation of reactive oxygen species (ROS). These entities are able to oxidize almost all classes of macromolecules, including proteins, lipidsThe metabolism of oxygen in aerobic organisms leads to generation of reactive oxygen species (ROS). These entities are able to oxidize almost all classes of macromolecules, including proteins, lipids and nucleic acids. The physiological level of ROS is usually regulated by antioxidant defense mechanisms. There are at least three groups of antioxidant enzymes: superoxide dismutases, catalases and glutathione peroxidases (GSH-Pxs) which neutralize ROS. The trace elements (copper, zinc and selenium) bound to the active sites of the above listed enzymes play an important role in the antioxidant defense system. In mammals, a major function of selenium (Se) and Se-dependent GSH-Pxs is to protect cells from oxidative stress. Selenium concentrations and GSH-Px activities are altered in blood components of chronic kidney disease (CKD) patients. The Se level is frequently lower than in healthy subjects and the concentration very often decreases gradually with advancing stage of the disease. Studies on red cell GSH-Px activity in CKD patients reported its values significantly lower, significantly higher and lower or higher, but not significantly as compared with healthy subjects. On the other hand, all authors who studied plasma GSH-Px activity have shown significantly lower values than in healthy subjects. The degree of the reduction decreases gradually with the progression of the disease. High inverse correlations were seen between plasma GSH-Px activity and creatinine level. A gradual decrease in plasma GSH-Px activity in CKD patients is due to the fact that this enzyme is synthesized predominantly in the kidney and thus the impairment of this organ is the cause of the enzyme's lower activity. Se supplementation to CKD patients has a slightly positive effect in the incipient stage of the disease, but usually no effect was observed in end-stage CKD. Presently, kidney transplantation is the only treatment that may restore plasma Se level and GSH-Px activity in patients suffering from end-stage CKD. A few studies have shown that in kidney recipients, plasma Se concentration and GSH-Px activity are restored to normal values within a period of 2 weeks to 3 months following surgery and thus it can be acknowledged that Se supplementation to those patients has a positive effect on plasma GSH-Px activity.

• Roles of reactive oxygen species and selected antioxidants in regulation of cellular metabolism.

  Authors: Małgorzata Stańczyk, Jolanta Gromadzińska, Wojciech Wasowicz

  International journal of occupational medicine and environmental health. 02/2005; 18(1):15-26.

  Reactive oxygen species (ROS) are essential for life of aerobic organisms. They are produced in normal cells and formed as a result of exposure to numerous factors, both chemical and physical. InReactive oxygen species (ROS) are essential for life of aerobic organisms. They are produced in normal cells and formed as a result of exposure to numerous factors, both chemical and physical. In normal cells, oxygen derivatives are neutralized or eliminated owing to the presence of a natural defense mechanism that involves enzymatic antioxidants (glutathione peroxidase, superoxide dismutase, catalase) and water or fat-soluble non-enzymatic antioxidants (vitamins C and E, glutathione, selenium). Under certain conditions, however, ROS production during cellular metabolism also stimulated by external agents may exceed the natural ability of cells to eliminate them from the organism. The disturbed balance leads to the state known as oxidative stress inducing damage of DNA, proteins, and lipids. An inefficient repair mechanism may finally trigger the process of neoplastic transformation or cell death. Reactive oxygen species are also an integral part of signal transduction essential for intercellular communication. The balance between pro- and antioxidative processes determines normal cellular metabolism manifested by genes activation and/or proteins expression in response to exo- and endogenous stimuli.

• The effects of melatonin on glutathione peroxidase activity in serum and erythrocytes after adriamycin in normal and pinealectomised rats.

  Authors: Katarzyna Dabrowska, Michał Stuss, Jolanta Gromadzińska, Wojciech Wasowicz, Ewa Sewerynek

  Endokrynologia Polska. 59(3):200-6.

  Introduction: Adriamycin (ADR) is a potent chemotherapeutic agent, effective in the treatment of leukaemias, lymphomas and many solid tumours. However, its clinical usage is often limited byIntroduction: Adriamycin (ADR) is a potent chemotherapeutic agent, effective in the treatment of leukaemias, lymphomas and many solid tumours. However, its clinical usage is often limited by cardiotoxicity, induced by oxygen radical damage of the membrane lipids. Melatonin (MEL) is a well-known antioxidant. It has been shown that MEL can scavenge free radicals, both directly and indirectly, stimulating the activity of antioxidative enzymes such as glutathione peroxidase (GSH-Px). The aim of the study: The aim of the study was to examine the effect of MEL on serum and erythrocyte GSH-Px activity after ADR in normal and pinealectomised rats. Material and methods: Wistar rats were divided into the three groups: control animals (Intact), sham-operated (Sham-PX) and pinealectomised (Px). Each of the groups was divided into four subgroups, injected with: 1 - saline, 2 - MEL, 3 - ADR and 4 - ADR + MEL. ADR was administered 2 months after Px as a single dose (15 mg/kg, i.p.) 1 hour after the fourth melatonin injection. Melatonin (5 mg/kg, i.p.) was administered for 4 days before and 2 days after ADR. After 6 days of treatment, the rats were killed by decapitation. Their blood was collected for measurements. Results: In serum GSH-Px activity decreased in all the groups after ADR. Pinealectomy decreased the activity of the enzyme in all the groups of animals examined. In erythrocytes GSH-Px decreased after ADR in the Px-animals. The effect of pinealectomy on erythrocyte GSH-Px activity was not as strongly expressed as serum GSH-Px activity. MEL did not change GSH-Px activity after ADR. Conclusion: Melatonin, in pharmacological concentrations, did not influence the activity of GSH-Px, either in normal or in pinealectomised rats after ADR. A deficiency of endogenous melatonin production may inhibit GSH-Px activity.

• Carcinogenic effect of arsenate in C57BL/6J/Han mice and its modulation by different dietary selenium status

  Authors: Maciej Stępnik, Jan Stetkiewicz, Aleksander Krajnow, Katarzyna Domeradzka, Dobrosława Gradecka-Meesters, Joanna Arkusz, Małgorzata Stańczyk, Jadwiga Palus, Elżbieta Dziubałtowska, Wojciech Sobala, Jolanta Gromadzińska, Wojciech Wąsowicz, Konrad Rydzyński

  Ecotoxicology and Environmental Safety.

  In this study, carcinogenic effects of arsenate in female C57BL/6J/Han mice exposed in drinking water to 50, 200 or 500 μg As/L for 24 months were investigated. All animals were fed low-seleniumIn this study, carcinogenic effects of arsenate in female C57BL/6J/Han mice exposed in drinking water to 50, 200 or 500 μg As/L for 24 months were investigated. All animals were fed low-selenium diet, however half of them were supplemented with sodium selenite in drinking water (200 μg Se/L) to ensure the normal dietary level of selenium. Glutathione peroxidase activity in erythrocytes and plasma as well as selenium concentration in plasma after 3, 6, 12 and 18 months in satellite groups showed considerable decrease in animals from non-selenium supplemented groups in comparison to supplemented groups. A clear arsenic concentration-dependent increase in the number of malignant lymphoma associated with increase in the risk of death was observed (hazard ratio=0.91, 1.46, and 2.24, for 50, 200 and 500 μg As/L, respectively). No significant influence of selenium dietary status on arsenic carcinogenicity was shown. A significant association between selenium supplementation status and increased risk of death of the animals from causes other than malignant tumors was found (HR=1.79, p=0.04).