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Wyświetlanie 1-8 z 8
Tytuł:
Wykorzystanie spektrometrii mas do analizy modyfikacji nukleotydów i adduktów DNA
Application of mass spectrometry methods for analysis of modified nucleotides and DNA adducts
Autorzy:
Hanus, J.
Jelonek, K.
Pietrowska, M.
Powiązania:
https://bibliotekanauki.pl/articles/171867.pdf
Data publikacji:
2011
Wydawca:
Polskie Towarzystwo Chemiczne
Tematy:
kancerogeneza
diagnostyka molekularna
spektrometria mas
nukleotydy
uszkodzenia DNA
addukty DNA
metylacja DNA
carcinogenesis
molecular diagnostics
mass spectrometry
nucleotides
DNA damage
DNA adducts
DNA methylation
Opis:
Chemically modified nucleotides, which are not normally present in genetic material, are called DN A adducts. This type of DN A modifications (damage) is directly related to processes of mutagenesis and carcinogenesis. Elevated levels of DN A adducts present in genetic material reflect exposure of humans to carcinogenic factors and are markers of increased risk of cancer [1]. For this reason different methods useful for quantitative and qualitative analyses of DN A adducts are used in the field of cancer prevention and research (Tab. 1). Enzymatically-catalyzed methylation of cytosine, observed mostly in so called CpG islands, is a frequent endogenous modification of genetic material. Such a DN A methylation is a key factor involved in regulation of gene expression, and methylation status of oncogenes and tumor supressor genes is an important biomarker of carcinogenesis. As such, analytical methods for assessment of DN A methylation are of great importance for molecular diagnostics of cancer. During the last decade significant progress has been made in methods available for quantitative, qualitative and structural analyses of biological molecules. Among intensively developed tools for bioanalyses are methods of mass spectrometry. Spectrometers that are based on two methods of ionization, namely electrospray ionization (ESI ) [30] and matrix-assisted laser desorption-ionization (MALDI ) [48], are particularly suitable for analyses of biological macromolecules: proteins and nucleic acids. Currently available mass spectrometers, together with microscale methods for sample preparation and separation, significantly increased sensitivity and accessible mass range of analyses. New generation of “user-friendly” instruments is developed to bring the techniques directly into the workplaces of biological and clinical investigators. This review demonstrates representative examples of mass spectrometry techniques used for qualitative analyses of nucleotide modifications and adducts present in genetic material of humans. In this field several methods base on spectrometers with electrospray ionization. Generated ions are separated according to their mass-to-charge ratio in an analyzer by electric fields; among different ion analyzers frequently used in this methods are single or triple quadrupole and ion traps (Fig. 1). Among other methods available for assessment of DN A adducts is so called Accelerator Mass Spectrometry (Fig. 2) [41]. The most frequently applied method for the assessment of DN A methylation is based on methylation-specific PCR reaction. Products of such PCR reactions are analyzed using MALDI mass spectrometry [54] (Fig. 3). In summary, new powerful methods of mass spectrometry that made available qualitative analyses of damage and modifications of human genetic material found their important place in modern biological and medical laboratories.
Źródło:
Wiadomości Chemiczne; 2011, 65, 3-4; 191-205
0043-5104
2300-0295
Pojawia się w:
Wiadomości Chemiczne
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Sperm quality and DNA integrity of coke oven workers exposed to polycyclic aromatic hydrocarbons
Autorzy:
Jeng, Hueiwang Anna
Pan, Chih-Hong
Chao, Mu-Rong
Chiu, Chien-Chih
Zhou, Guodong
Chou, Chon-Kit
Lin, Wen-Yi
Powiązania:
https://bibliotekanauki.pl/articles/2168377.pdf
Data publikacji:
2016-11-18
Wydawca:
Instytut Medycyny Pracy im. prof. dra Jerzego Nofera w Łodzi
Tematy:
DNA damage
semen quality
sperm
DNA integrity
DNA fragmentation
bulky DNA adducts
Opis:
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
Źródło:
International Journal of Occupational Medicine and Environmental Health; 2016, 29, 6; 915-926
1232-1087
1896-494X
Pojawia się w:
International Journal of Occupational Medicine and Environmental Health
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Sequence-specific p53 gene damage by chloroacetaldehyde and its repair kinetics in Escherichia coli
Autorzy:
Kowalczyk, Paweł
Cieśla, Jarosław
Saparbaev, Murat
Laval, Jacques
Tudek, Barbara
Powiązania:
https://bibliotekanauki.pl/articles/1041247.pdf
Data publikacji:
2006
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
chloroacetaldehyde
p53
replication
exocyclic DNA adducts
vinyl chloride
LM-PCR
DNA repair
sequence-specific DNA damage
Opis:
Oxidative stress and certain environmental carcinogens, e.g. vinyl chloride and its metabolite chloroacetaldehyde (CAA), introduce promutagenic exocyclic adducts into DNA, among them 1,N6-ethenoadenine (εA), 3,N4-ethenocytosine (εC) and N2,3-ethenoguanine (εG). We studied sequence-specific interaction of the vinyl-chloride metabolite CAA with human p53 gene exons 5-8, using DNA Polymerase Fingerprint Analysis (DPFA), and identified sites of the highest sensitivity. CAA-induced DNA damage was more extensive in p53 regions which revealed secondary structure perturbations, and were localized in regions of mutation hot-spots. These perturbations inhibited DNA synthesis on undamaged template. We also studied the repair kinetics of CAA-induced DNA lesions in E. coli at nucleotide resolution level. A plasmid bearing full length cDNA of human p53 gene was modified in vitro with 360 mM CAA and transformed into E. coli DH5α strain, in which the adaptive response system had been induced by MMS treatment before the cells were made competent. Following transformation, plasmids were re-isolated from transformed cultures 35, 40, 50 min and 1-24 h after transformation, and further subjected to LM-PCR, using ANPG, MUG and Fpg glycosylases to identify the sites of DNA damage. In adaptive response-induced E. coli cells the majority of DNA lesions recognized by ANPG glycosylase were removed from plasmid DNA within 35 min, while MUG glycosylase excised base modifications only within 50 min, both in a sequence-dependent manner. In non-adapted cells resolution of plasmid topological forms was perturbed, suggesting inhibition of one or more bacterial topoisomerases by unrepaired ε-adducts. We also observed delayed consequences of DNA modification with CAA, manifesting as secondary DNA breaks, which appeared 3 h after transformation of damaged DNA into E. coli, and were repaired after 24 h.
Źródło:
Acta Biochimica Polonica; 2006, 53, 2; 337-347
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Recognition and repair of DNA-cisplatin adducts.
Autorzy:
Woźniak, Katarzyna
Błasiak, Janusz
Powiązania:
https://bibliotekanauki.pl/articles/1043720.pdf
Data publikacji:
2002
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
DNA-protein crosslinks
cisplatin
DNA adducts
DNA damage
DNA repair
cis-diamminedichloroplatinum
Opis:
Anticancer activity of cisplatin (cis-diamminedichloroplatinum) is believed to result from its interaction with DNA. The drug reacts with nucleophilic sites in DNA forming monoadducts as well as intra- and interstrand crosslinks. DNA-cisplatin adducts are specifically recognized by several proteins. They can be divided into two classes. One constitutes proteins which recognize DNA damage as an initial step of the nucleotide excision and mismatch repair pathways. The other class contains proteins stabilizing cellular DNA-protein and protein-protein complexes, including non-histone proteins from the HMG (high-mobility-group) family. They specifically recognize 1,2-interstrand d(GpG) and d(ApG) crosslinks of DNA-cisplatin adducts and inhibit their repair. Many HMG-domain proteins can function as transcription factors, e.g. UBF, an RNA polymerase I transcription factor, the mammalian testis-determining factor SRY and the human mitochondrial transcription factor mtTFA. Moreover, it seems that some proteins, which probably recognize DNA-cisplatin adducts non-specifically, e.g. actin and other nuclear matrix proteins, can disturb the structural and functional organization of the nucleus and whole cell. The formation of complexes between DNA and proteins in the presence of cisplatin and the changes in the cell architecture may account for the drug cytotoxicity.
Źródło:
Acta Biochimica Polonica; 2002, 49, 3; 583-596
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Mismatch dependent uracil/thymine-DNA glycosylases excise exocyclic hydroxyethano and hydroxypropano cytosine adducts.
Autorzy:
Borys-Brzywczy, Ewa
Arczewska, Katarzyna
Saparbaev, Murat
Hardeland, Ulrike
Schär, Primo
Kuśmierek, Jarosław
Powiązania:
https://bibliotekanauki.pl/articles/1041473.pdf
Data publikacji:
2005
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
base excision repair
E. coli mismatch uracil-DNA glycosylase
exocyclic cytosine adducts
human thymine-DNA glycosylase
S. pombe Thp1p glycosylase
Opis:
Exocyclic adducts of DNA bases, such as etheno- and hydroxyalkano- ones, are generated by a variety of bifunctional agents, including endogenously formed products of lipid peroxidation. In this work we selectively modified cytosines in the 5'-d(TTT TTT CTT TTT CTT TTT CTT TTT T)-3' oligonucleotide using: chloroacetaldehyde to obtain 3,N4-α-hydroxyethano- (HEC) and 3,N4-etheno- (εC), acrolein to obtain 3,N4-α-hydroxypropano- (HPC) and crotonaldehyde to obtain 3,N4-α-hydroxy-γ-methylpropano- (mHPC) adducts of cytosine. The studied adducts are alkali-labile which results in oligonucleotide strain breaks at the sites of modification upon strong base treatment. The oligonucleotides carrying adducted cytosines were studied as substrates of Escherichia coli Mug, human TDG and fission yeast Thp1p glycosylases. All the adducts studied are excised by bacterial Mug although with various efficiency: εC >HEC >HPC >mHPC. The yeast enzyme excises efficiently εC ł HEC >HPC, whereas the human enzyme excises only εC. The pH-dependence curves of excision of εC, HEC and HPC by Mug are bell shaped and the most efficient excision of adducts occurs within the pH range of 8.6-9.6. The observed increase of excision of HEC and HPC above pH 7.2 can be explained by deprotonation of these adducts, which are high pKa compounds and exist in a protonated form at neutrality. On the other hand, since εC is in a neutral form in the pH range studied, we postulate an involvement of an additional catalytic factor. We hypothesize that the enzyme structure undergoes a pH-induced rearrangement allowing the participation of Lys68 of Mug in catalysis via a hydrogen bond interaction of its ε-amino group with N4 of the cytosine exocyclic adducts.
Źródło:
Acta Biochimica Polonica; 2005, 52, 1; 149-165
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
High levels of bulky DNA adducts in human sperm correlate with impaired fertility.
Autorzy:
Horak, Stanisław
Polańska, Joanna
Widłak, Piotr
Powiązania:
https://bibliotekanauki.pl/articles/1043666.pdf
Data publikacji:
2003
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
fertility
spermatozoa
human
DNA damage
adducts
32P-postlabelling
Opis:
Progressive decline in fertility and sperm quality has been reported over the last few decades, especially in industrialized nations. It has been proposed that exposure to factors that induce damage in DNA of spermatogenic cells may significantly contribute to impaired fertility. Here, the 32P-postlabelling method was used to analyze the levels of bulky DNA adducts in sperm cells in a group of 179 volunteers, either healthy subjects or patients with an impaired fertility. The levels of DNA adducts were 1.35-fold higher in the infertile group as compared to healthy individuals (P = 0.012). Similarly, a significant negative correlation between the levels of DNA adducts and measures of semen quality (sperm concentration and motility) has been observed (P Ł 0.001). In addition, the levels of bulky DNA adducts in sperm cells positively correlates with amounts of leukocytes in semen, which were significantly higher in semen of infertile subjects.
Źródło:
Acta Biochimica Polonica; 2003, 50, 1; 197-203
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Effect of the GSTM1 genotype on the biomarkers of exposure to polycyclic aromatic hydrocarbons: Meta-analysis
Autorzy:
Li, Dandan
Wang, Bingling
Feng, Guochang
Xie, Meng
Wang, Lijuan
Gao, Ruqin
Powiązania:
https://bibliotekanauki.pl/articles/2161849.pdf
Data publikacji:
2017-03-30
Wydawca:
Instytut Medycyny Pracy im. prof. dra Jerzego Nofera w Łodzi
Tematy:
polymorphism
micronuclei
meta-analysis
1-hydroxypyrene
DNA adducts
GSTM1
Opis:
The role of glutathione S-transferase Mu 1 (GSTM1) in the biomonitoring of polycyclic aromatic hydrocarbons (PAHs) is not clear. Our purpose has been to evaluate the influence of GSTM1 genotypes on 1-hydroxypyrene (1-OHP), deoxyribonucleic acid (DNA) adducts, and micronucleus frequency in both occupational and non-occupational populations of null and active GSTM1 carriers. We conducted a meta-analysis on 25 articles that met our strict inclusion criteria (11 studies on 1-OHP, 9 on DNA adducts, and 5 on the micronucleus frequency). In the case of occupationally exposed workers, micronucleus frequency was only significantly higher in the null GSTM1 carriers than in the active GSTM1 carriers. In the non-occupationally exposed general population, 1-OHP and micronucleus frequency were significantly higher in the null GSTM1 carriers. The results of Egger’s test and funnel plot analysis indicated no significant publication bias. In conclusion, GSTM1 genotypes may affect the urinary 1-OHP in the non-occupationally exposed general population, and micronucleus frequency in both occupational workers and non-occupational population. Int J Occup Med Environ Health 2017;30(2):177–201
Źródło:
International Journal of Occupational Medicine and Environmental Health; 2017, 30, 2; 177-201
1232-1087
1896-494X
Pojawia się w:
International Journal of Occupational Medicine and Environmental Health
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
DNA damage and alterations of gene expression in chronic-degenerative diseases.
Autorzy:
Izzotti, Alberto
Powiązania:
https://bibliotekanauki.pl/articles/1043658.pdf
Data publikacji:
2003
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
multigene expression analysis
DNA adducts
human trabecular meshwork
light
cigarette smoke
UV
glaucoma
cDNA array
Opis:
Chronic-degenerative diseases (CDD) recognise a variety of exogenous and endogenous risk factors interacting with the organism for many years before disease onset. We applied genomic and postgenomic molecular analyses in experimental models characterised by different contribution of exogenous and endogenous CDD risk factors. Exposure of mice to halogen light for 28 days resulted in induction of cyclobutane dimers and oxidative DNA damage in the skin. Evaluation of postgenomic alterations by cDNA arrays revealed upregulation of DNA repair pathways, increased cell division rate and protooncogenes transcription, resulting in skin tumors, 1 year later. Exposure of p53-/+ mutant mice to cigarette smoke (CS) for 28 days induced DNA adducts formation in the lung. Postgenomic alterations included decreased apoptosis and increased cell division, as compared to CS-exposed wild type mice. These phenomena resulted in lung tumors, 9 months later. Transplacental exposure of mouse foetuses to cigarette smoke induced DNA adduct formation in the liver. cDNA arrays analyses demonstrated decreased cell division, apoptosis increase, and tissue hypoxia. These phenomena resulted in growth retardation of the whole organism. Molecular alterations were investigated in human trabecular meshwork, the non-replicating ocular epithelia involved in the pathogenesis of chronic degenerative glaucoma. Results indicate increased oxidative DNA damage in glaucoma patients as compared to unaffected controls. These four experimental studies suggest that DNA damage may result in different CDD (cancer, growth retardation, glaucoma) depending on the replication rate of the target cell population.
Źródło:
Acta Biochimica Polonica; 2003, 50, 1; 145-154
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
    Wyświetlanie 1-8 z 8

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