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EN
Objectives: The urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) was used as a biomarker of oxidative DNA damage. The urinary 8-oxodG levels in petrol filling station attendants (exposed) at various petrol bunks were estimated as well as in the unexposed (cashier) population. Materials and Methods: A total of 100 workers (79 petrol fillers and 21 cashiers) aged from 20 to 41 years participated in the study. An informed consent was taken from each participant. Information on personal habits and health was obtained through a questionnaire. After shifts, urine samples were collected analyzed for 8-oxodG using enzyme-linked immunosorbent assay (ELISA). Results: Fifty-three percent of workers were in the 21-30 years age group. The maximum level of 8-oxodG was observed in the age group ≥ 41 years and the minimum in the age group of 31-40 years. The maximum level of 8-oxodG was observed among those workers who had ≥ 21 years of experience. The concentrations of 8-oxodG were significantly higher in petrol fillers than those in cashiers (p < 0.05). Conclusions: Despite the conflicting results obtained in our study it was shown that 8-oxodG is related to chemical exposure. Further research is needed embracing a bigger number of participants to highlight the correlations between the exposure and the effects.
EN
Objectives: The aim of this study was to investigate the cyto- and genotoxicity of nanocomposites (NCs) and generation of reactive oxygen species (ROS) as a result of particle-cell interactions. Materials and Methods: Titanium dioxide (TiO₂-Ag) and ion-exchange resin (Res-Ag), both coated with silver (Ag), were examined. The murine macrophage J774A.1 cells were incubated in vitro with NC at different concentrations for 24 h. Cytotoxicity was analyzed by the methylthiazolyldiphenyltetrazolium bromide reduction test (MTT reduction test). ROS generation was assessed by incubation of cells with dichlorodihydrofl uorescein diacetate (DCF) and fl ow cytometry. DNA damage was detected by comet assay and included single-strand breaks (SSB), alkali-labile sites (ALS) and oxidative DNA damage after formamidopyrimidine glycosylase (FPG) treatment. The tail moment was used as an indicator of DNA damage. Results: TiO₂-Ag was not cytotoxic up to 200 μg/ml, whereas IC₅₀ for Res-Ag was found to be 23 μg/ml. Intracellular ROS levels were elevated after 4 h of exposure to Res-Ag at the concentration of 50 μg/ml. Both types of NC induced fragmentation of DNA strands, but only one of the composites caused damage to purine bases. TiO₂-Ag induced SSB of DNA at concentrations of 10 and 5 μg/ml. For Res-Ag, a concentration-dependent increase in tail moments was observed. Conclusions: Silver-coated nanocomposites (both TiO₂- Ag and Res-Ag) may cause genotoxic effects in murine macrophages J774A.1. Res-Ag increased generation of ROS which suggested that toxicity of Res-Ag in murine macrophages is likely to be mediated through oxidative stress. This paper will support industry and regulators alike in the assessment of hazards and risks and methods for their mitigation at the earliest possible stage in material and product development.
EN
Objectives The objective of this study was to assess sperm quality and deoxyribonucleic acid (DNA) integrity of coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs) as compared to control subjects. Material and methods The coke oven workers (N = 52) and administrative staff (N = 35) of a steel plant served as the exposed and control groups, respectively. Exposure to PAHs was assessed by measuring 1-hydroxypyren. Analysis of sperm quality (concentration, motility, vitality, and morphology) was performed simultaneously with sperm DNA integrity analysis, including DNA fragmentation, denaturation, bulky DNA adducts, and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxo-dGuo). A questionnaire was conducted to collect demographic and potential confounding data. Results The coke oven workers had lower percentages of sperm motility, vitality and normal morphology than the control group, but the difference was not significant. For DNA integrity, the coke oven workers had significantly higher concentrations of bulky DNA adducts and 8-oxo-dGuo than the control subjects (p = 0.009 and p = 0.048, respectively). However, DNA fragmentation percentages did not significantly increase as compared to those in the subjects from the control group (p = 0.232). There was no correlation between sperm quality parameters and DNA integrity indicators. Conclusions Occupational exposure of the coke oven workers to PAHs was associated with decreased sperm DNA integrity. Int J Occup Med Environ Health 2016;29(6):915–926
EN
Objectives This study aimed to evaluate cytogenetic damage in the buccal mucosa of non-exposed subjects (N = 33) and insecticide-exposed fumigators (N = 31) in the urban area of Cali, Colombia. Material and Methods Through a questionnaire sociodemographic data, anthropometric measurements, state of health, and lifestyle were collected. Buccal micronucleus cytome (BMCyt) assay was using for evaluate cytogenetic damage. Results The study showed that all fumigators used adequate personal protective equipment (PPE) and had low alcohol consumption. The authors did not find significant differences in BMCyt biomarkers between the groups (p > 0.05). Multivariate analysis showed a 13% increase in micronucleus (MN) frequency for every year of increasing age (OR = 1.13, p = 0.029), and higher MN with the decrease in daily fruit consumption (OR = 4.71, p = 0.084), without statistical significance. Conclusions The results between groups could be related to healthy habits and PPE use among the subjects.
PL
Wprowadzenie: Składnik zielonej herbaty – galusan epigallokatechiny (EGCG) – znany jest ze swoich właściwości chemoprewencyjnych i chemoterapeutycznych. Wykazuje silne właściwości antyoksydacyjne i przeciwzapalne, a w stosunku do komórek nowotworowych – działanie antyproliferacyjne lub proapoptotyczne. Etopozyd jest jednym z najczęściej stosowanych leków przeciwnowotworowych, wywołującym jednak wiele skutków ubocznych. Materiały i metody: W eksperymentach in vitro badano potencjalną rolę EGCG w terapii skojarzonej z etopozydem w leczeniu przewlekłej białaczki szpikowej. Komórki ustalonej linii białaczkowej K562 poddano działaniu etopozydu i/lub EGCG w celu określenia wpływu EGCG na przeżywalność komórek, poziom uszkodzeń DNA oraz częstość procesu apoptozy. Poziom uszkodzeń DNA mierzono przy pomocy elektroforezy pojedynczych komórek w żelu agarozowym (test kometowy), natomiast apoptozę oceniano pod mikroskopem fluorescencyjnym z użyciem barwnika Hoechst 33342. Wyniki: Uzyskane wyniki badań wskazują, że EGCG w stężeniu 50 i 100 μM uwrażliwia komórki białaczkowe na cytotoksyczne działanie etopozydu, zwiększając poziom uszkodzeń DNA i częstość apoptozy. Wnioski: Dane wskazują, że galusan epigallokatechiny może się okazać skutecznym polifenolem w terapii skojarzonej z etopozydem w leczeniu przewlekłej białaczki szpikowej
EN
Introduction: Green tea ingredient – epigallocatechin gallate (EGCG) – is known for its chemopreventive and chemotherapeutic properties. It has strong antioxidant and anti-inflammatory properties, and antiproliferative or pro-apoptotic activity against cancer cells. Etoposide is one of the most commonly used anti-cancer drugs causing many side effects. Materials and methods: This study investigated the role of EGCG in combination therapy with etoposide in the treatment of chronic myeloid leukemia. K562 cells were treated with EGCG and / or etoposide to determine the effect of this polyphenol on cell survival, DNA damage or apoptosis. DNA damages were measured with single cell gel electrophoresis (comet assay) and the apoptosis were analyzed in fluorescence microscope with Hoechst 33342 staining. Results: Preliminary results suggest that EGCG at 50 and 100 μM sensitizes leukemic cells to the cytotoxic effect of etoposide, increases DNA damage that promotes removal cell and directs them to apoptosis. Conclusions: The data show that epigallocatechin gallate may prove to be an effective polyphenol in combination therapy with etoposide in the treatment of chronic myeloid leukemia. However, further research is needed to explain the EGCG interaction with chemotherapeutics.
PL
Wprowadzenie: Żywność zawiera potencjalnie mutagenne substancje, takie jak PhIP, heterocykliczna amina aromatyczna powstająca podczas obróbki cieplnej mięsa, jak również substancje mogące działać w sposób ochronny poprzez m.in. modulowanie odpowiedzi antyoksydacyjnej i przeciwzapalnej, jak np. kurkumina, która jest obecna w kurkumie i mieszance curry. Materiał i metody: W przedstawionych badaniach analizowano rolę PhIP i kurkuminy na uszkodzenia DNA w limfocytach izolowanych z krwi pacjentów z rakiem jelita grubego. Limfocyty osób z rakiem jelita grubego (10 pacjentów) oraz zdrowych (kontrola, 6 osób) traktowano PhIP i/lub kurkuminą, następnie poziom uszkodzeń DNA porównano metodą kometową. Wyniki: Wstępne wyniki sugerują, że limfocyty chorych na nowotwór jelita grubego mają większe podstawowe uszkodzenia DNA niż te od osób zdrowych. Uszkodzenia wywoływane PhIP są liniowo zależne od zastosowanej dawki i mogą być zredukowane w obecności kurkuminy (zwłaszcza w stężeniu do 5 μM). Wnioski: Dane wskazują, że kurkumina może wywierać działanie ochronne przed uszkodzeniami DNA indukowanymi mutagenem obecnym w żywności.
EN
Introduction: Food contains substances that are potentially mutagens such as PhIP, heterocyclic aromatic amine, produced during heat treatment of meat, as well as substances that may act in protective manner, inter alia by modulating the antioxidant and anti-infl ammatory response, such as curcumin, which is present in turmeric and curry. Material and methods: This study investigated the effect of PhIP and curcumin on DNA damage in lymphocytes isolated from the blood of colorectal cancer patients. Lymphocytes from individuals diagnosed with colorectal cancer (N=10) and healthy individuals (control, N=6) were treated with PhIP or/and curcumin, followed by analysis of DNA damage using single cell gel electrophoresis (comet assay). Results: Preliminary results suggest that lymphocytes of patients with colorectal cancer have a greater baseline DNA damage than those from healthy individuals. PhIP-induced DNA damage is dose-dependent and can be reduced in the presence of curcumin, especially at low concentration (up to 5 μM). Conclusions: The data show that curcumin may exert a protective effect against DNA damage induced by mutagens present in food.
EN
Genetic polymorphism is associated with the occurrence of at least 2 different alleles in the locus with a frequency higher than 1% in the population. Among polymorphisms we can find single nucleotide polymorphism (SNP) and polymorphism of variable number of tandem repeats. The presence of certain polymorphisms in genes encoding DNA repair enzymes is associated with the speed and efficiency of DNA repair and can protect or expose humans to the effects provoked by xenobiotics. Chemicals, such as lead, arsenic pesticides are considered to exhibit strong toxicity. There are many different polymorphisms in genes encoding DNA repair enzymes, which determine the speed and efficiency of DNA damage repair induced by these xenobiotics. In the case of lead, the influence of various polymorphisms, such as APE1 (apurinic/apyrimidinic endonuclease 1) (rs1130409), hOGG1 (human 8-oxoguanine glycosylase) (rs1052133), XRCC1 (X-ray repair cross-complementing protein group 1) (rs25487), XRCC1 (rs1799782) and XRCC3 (X-ray repair cross-complementing protein group 3) (rs861539) were described. For arsenic polymorphisms, such as ERCC2 (excision repair cross-complementing) (rs13181), XRCC3 (rs861539), APE1 (rs1130409) and hOGG1 (rs1052133) were examined. As to pesticides, separate and combined effects of polymorphisms in genes encoding DNA repair enzymes, such as XRCC1 (rs1799782), hOGG1 (rs1052133), XRCC4 (X-ray repair cross-complementing protein group 4) (rs28360135) and the gene encoding the detoxification enzyme PON1 paraoxonase (rs662) were reported. Med Pr 2018;69(2):225–235
PL
Polimorfizm genetyczny wiąże się z występowaniem w populacji co najmniej 2 różnych alleli w danym locus z częstością większą niż 1%. Wyróżniamy m.in. polimorfizm pojedynczego nukleotydu (single nucleotide polymorphism – SNP) i polimorfizm zmiennej liczby powtórzeń tandemowych. Występowanie określonych polimorfizmów w genach kodujących enzymy naprawy DNA jest związane z szybkością i wydajnością naprawy DNA oraz może chronić lub narażać daną osobę na skutki działania określonego ksenobiotyku. Związki chemiczne takie, jak ołów, arsen i pestycydy odznaczają się dużą toksycznością. Opisano wiele różnych polimorfizmów genów kodujących enzymy naprawy DNA, które mają wpływ na skuteczność naprawy uszkodzeń DNA indukowanych przez te ksenobiotyki. W przypadku ołowiu zbadano wpływ polimorfizmów genów: APE1 (apurinic/apyrimidinic endonuclease 1 – endonukleaza miejsca apurynowego/apirymidynowego) (rs1130409), hOGG1 (human 8-oxoguanine glycosylase – glikozylaza 8-oksyguaniny) (rs1052133), XRCC1 (X-ray repair cross-complementing protein group 1 – białko biorące udział w naprawie DNA przez wycinanie zasad) (rs25487), XRCC1 (rs1799782) oraz XRCC3 (X-ray repair cross-complementing protein group 3 – białko biorące udział w naprawie DNA przez rekombinację homologiczną) (rs861539). Dla arsenu przedstawiono w niniejszej pracy wyniki badań dotyczących następujących polimorfizmów: ERCC2 (excision repair cross-complementing – białko biorące udział w naprawie DNA przez wycinanie nukleotydów) (rs13181), XRCC3 (rs861539), APE1 (rs1130409) oraz hOGG1 (rs1052133). W odniesieniu do pestycydów w pracy przedstawiono zarówno osobny, jak i łączny wpływ polimorfizmów genów takich, jak XRCC1 (rs1799782), hOGG1 (rs1052133), XRCC4 (X-ray repair cross-complementing protein group 4 – białko biorące udział w naprawie DNA przez łączenie końców niehomologicznych) (rs28360135) i genu kodującego enzym detoksykacyjny paraoksonazę PON1 (paraoxonase 1) (rs662). Med. Pr. 2018;69(2):225–235
EN
Ultraviolet radiation is a physical mutagenic and cancerogenic factor. About 95% of ultraviolet A (UVA) (320–400 nm) and 5% of UVB (280–320 nm) reach the Earth’s surface. Melanin is a natural skin protective factor against UV radiation. Skin cancers associated with long-term exposure to UV radiation are: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). The high risk of BCC development is related to acute and repeated exposure to UV causing sunburn. Molecular studies of BBC demonstrated disorders in sonic hedgehog (SHH) cell signaling regulation pathway, associated with the suppressor protein patched homolog 1 gene (PTCH1) mutations. The risk of the BCC development is related to the polymorphism of melanokortin-1 receptor gene (MC1R). Tumor P53 gene mutations observed in BCC cells has been classified as secondary genetic changes. In SCC cells UV-induced mutations were mostly related to P53 gene. Increased expression of cyclooxigenase- 2 gene (COX-2) plays a significant role in the development of SCC. Other pathogenetic factors include intensification of the synthesis of pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin-1 α (IL-1α), IL-1β and IL-6). Currently, the role of UVB has been recognized in the pathogenesis of CMM. In CMM cells the following gene mutations were noted: cyclindependent kinase inhibitor 2A INK4A (p16 INK4A), cyclin-dependent kinase 4 (CDK4), Ras, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and proto-oncogene B-Raf (BRAF). The BRAF gene mutations were observed in ~50% of CMM cases. Mutations of P53 gene are not characteristic of CMM cells. Med Pr 2016;67(2):255–266
PL
Promieniowanie ultrafioletowe (UV) jest fizycznym czynnikiem mutagennym i karcynogennym. Do powierzchni Ziemi dociera ok. 95% promieniowania ultrafioletowego A (UVA) (320–400 nm) i ok. 5% UVB (280–320 nm). Naturalnym czynnikiem ochronnym skóry przed UV jest melanina. Do raków skóry, których rozwój jest związany z długotrwałym narażeniem na promieniowanie UV, zalicza się niebarwnikowe raki skóry (non-melanoma skin cancers – NMSC) – raka podstawnokomórkowego (basal cell carcinoma – BCC) i raka kolczystokomórkowego (squamous cell carcinoma – SCC) oraz czerniaka złośliwego skóry (cutaneous malignant melanoma – CMM). Wysokie ryzyko rozwoju BCC związane jest z ostrą i wielokrotną ekspozycją na UV, powodującą oparzenia słoneczne. Badania molekularne BCC wykazały zaburzenia na szlaku regulacji sygnalizacji komórkowej sonic hedgehog (SHH), które były związane z mutacjami genu supresorowego PTCH1 (protein patched homolog 1). Ryzyko rozwoju BCC jest również związane z polimorfizmem genu receptora melanokortyny-1 (MC1R). Obserwowane w komórkach BCC mutacje genu P53 klasyfikowano jako wtórne zmiany genetyczne. W komórkach SCC mutacje indukowane UV najczęściej dotyczyły genu P53. W rozwoju SCC istotne znaczenie ma zwiększona ekspresja genu enzymu cyklooksygenazy-2 (COX-2). Innym czynnikiem patogenetycznym SCC jest nasilenie syntezy cytokin prozapalnych (czynnika martwicy nowotworu α (tumor necrosis factor α – TNF-α), interleukiny-1 α (IL-1α), IL-1β i IL-6). Obecnie w patogenezie CMM powszechnie uznawana jest rola UVB. W komórkach CMM notowano mutacje w genach: p16 INK4A (cyclin-dependent kinase inhibitor 2A INK4A), genie kodującym cyklinozależną kinazę 4 (cyclin-dependent kinase 4 – CDK4), Ras, PTEN (phosphatase and tensin homolog deleted on chromosome 10) i BRAF (proto-oncogene B-Raf). Mutacje genu BRAF stwierdzano w ok. 50% przypadków CMM. Mutacje genu P53 nie są charakterystyczne dla komórek CMM. Med. Pr. 2016;67(2):255–266
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