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Tytuł:
A new look at adaptive mutations in bacteria.
Autorzy:
Janion, Celina
Powiązania:
https://bibliotekanauki.pl/articles/1044374.pdf
Data publikacji:
2000
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
adaptive mutations
DNA damage
DNA repair
Opis:
This is a short survey of the adaptive mutation processes that arise in non- or slowly- dividing bacterial cells and includes: (i) bacterial models in which adaptive mutations are studied; (ii) the mutagenic lesions from which these mutations derive; (iii) the influence of DNA repair processes on the spectrum of adaptive mutations. It is proposed that in starved cells, likely as during the MFD phenomenon, lesions in tRNA suppressor genes are preferentially repaired and no suppressor tRNAs are formed as a result of adaptive mutations. Perhaps the most provocative proposal is (iv) a hypothesis that the majority of adaptive mutations are selected in a pre-apoptotic state where the cells are either mutated, selected, and survive, or they die.
Źródło:
Acta Biochimica Polonica; 2000, 47, 2; 451-457
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Mutations in DNA polymerase gamma cause error prone DNA synthesis in human mitochondrial disorders
Autorzy:
Copeland, William
Ponamarev, Mikhail
Nguyen, Dinh
Kunkel, Thomas
Longley, Matthew
Powiązania:
https://bibliotekanauki.pl/articles/1043659.pdf
Data publikacji:
2003
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
aging
DNA replication
mitochondria
DNA repair
DNA polymerase
Opis:
This paper summarizes recent advances in understanding the links between the cell's ability to maintain integrity of its mitochondrial genome and mitochondrial genetic diseases. Human mitochondrial DNA is replicated by the two-subunit DNA polymerase γ (pol γ). We investigated the fidelity of DNA replication by pol γ with and without exonucleolytic proofreading and its p55 accessory subunit. Pol γ has high base substitution fidelity due to efficient base selection and exonucleolytic proofreading, but low frameshift fidelity when copying homopolymeric sequences longer than four nucleotides. Progressive external ophthalmoplegia (PEO) is a rare disease characterized by the accumulation of large deletions in mitochondrial DNA. Recently, several mutations in the polymerase and exonuclease domains of the human pol γ have been shown to be associated with PEO. We are analyzing the effect of these mutations on the human pol γ enzyme. In particular, three autosomal dominant mutations alter amino acids located within polymerase motif B of pol γ. These residues are highly conserved among family A DNA polymerases, which include T7 DNA polymerase and E. coli pol I. These PEO mutations have been generated in pol γ to analyze their effects on overall polymerase function as well as the effects on the fidelity of DNA synthesis. One mutation in particular, Y955C, was found in several families throughout Europe, including one Belgian family and five unrelated Italian families. The Y955C mutant pol γ retains a wild-type catalytic rate but suffers a 45-fold decrease in apparent binding affinity for the incoming dNTP. The Y955C derivative is also much less accurate than is wild-type pol γ, with error rates for certain mismatches elevated by 10- to 100-fold. The error prone DNA synthesis observed for the Y955C pol γ is consistent with the accumulation of mtDNA mutations in patients with PEO. The effects of other pol γ mutations associated with PEO are discussed.
Źródło:
Acta Biochimica Polonica; 2003, 50, 1; 155-167
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
The pH optimum of native uracil-DNA glycosylase of Archaeoglobus fulgidus compared to recombinant enzyme indicates adaption to cytosolic pH
Autorzy:
Knævelsrud, Ingeborg
Kazazic, Sabina
Birkeland, Nils-Kåre
Bjelland, Svein
Powiązania:
https://bibliotekanauki.pl/articles/1039311.pdf
Data publikacji:
2014
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
DNA repair
uracil-DNA glycosylase
uracil
deamination
hyperthermophiles
Opis:
Uracil-DNA glycosylase of Archaeoglobus fulgidus (Afung) in cell extracts exhibited maximal activity around pH 6.2 as compared to pH 4.8 for the purified recombinant enzyme expressed in Escherichia coli. Native Afung thus seems to be adapted to the intracellular pH of A. fulgidus, determined to be 7.0±0.1. Both recombinant and native Afung exhibited a broad temperature optimum for activity around 80°C, reflecting the A. fulgidus optimal growth temperature of 83°C. Adaption to the neutral conditions in the A. fulgidus cytoplasm might be due to covalent modifications or accessory factors, or due to a different folding when expressed in the native host.
Źródło:
Acta Biochimica Polonica; 2014, 61, 2; 393-395
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Impact of APEX Ile64val Gene Polymorphisms of DNA Repair Ber System on Modulation of the Risk of Colorectal Cancer in the Polish Population
Autorzy:
Kabziński, Jacek
Majsterek, Ireneusz
Mik, Michał
Dziki, Adam
Dziki, Łukasz
Maciejczak, Lucjan
Powiązania:
https://bibliotekanauki.pl/articles/1395566.pdf
Data publikacji:
2015-03-01
Wydawca:
Index Copernicus International
Tematy:
colorectal cancer
polymorphisms
APEX
DNA repair
Opis:
Colorectal cancer (CRC) is one of the deadliest cancers which lie in the incidence of morbidity in second place. Intensive research is to determine and confirm the genetic basis of this disease, which is believed may have a direct relationship with the reduced efficiency of DNA repair systems. The aim of this study was to determine the effect of APEX gene polymorphism Ile64Val on increasing the risk of colorectal cancer in the Polish population. Material and methods. The blood samples collected from 150 patients diagnosed with colon cancer was used. The control group consisted of 150 healthy subjects. Genotyping was performed by TaqMan method. Results. The results indicate that genotype Ile Val is associated with an increased risk of colorectal cancer (OR 2.069; 95% CI 1,205-3,552; p = 0.008). Conclusions. Based on these results, we conclude that the APEX gene polymorphism Ile64Val may be associated with an increased risk of colorectal cancer.
Źródło:
Polish Journal of Surgery; 2015, 87, 3; 121-123
0032-373X
2299-2847
Pojawia się w:
Polish Journal of Surgery
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Application of ionizing radiation in studies of biomarkers of individual susceptibility
Autorzy:
Cebulska-Wasilewska, A.
Powiązania:
https://bibliotekanauki.pl/articles/147794.pdf
Data publikacji:
2005
Wydawca:
Instytut Chemii i Techniki Jądrowej
Tematy:
biomarkers
susceptibility
application of radiation
DNA repair
Opis:
Human biomonitoring, as a tool to identify health risk from environmental exposures, has gained increasing interest especially in the areas of cancer risk assessment and diseases treatment. Chromosome aberrations resulting from direct DNA breakage or from inhibition of DNA repair or synthesis, measured in peripheral blood lymphocytes, have been used successfully in the assessment of health risk associated to environmental genotoxic exposures. A faster but sensitive and reliable method for detection of DNA damage, or DNA repair capacity, might be crucial to many fields from molecular epidemiology and toxicology to preventive and clinical medicine. There are reports that results of DNA measures with the use of single cell gel electrophoresis (SCGE) correlate, on the one hand, with physical measures of genotoxins, and on the other hand, with cytogenetic damage that is a biomarker associated to the alteration of the health risk. This review is based on studies in which exposure to radiation was applied as a challenging treatment and DNA damage induced and repaired was analyzed with the use of the alkaline version of SCGE assay. Results from studies on susceptibilities and repair competence carried out in various groups of exposed workers, controls, and cancer patients (more than 700 donors) show variability between donors both in a response to challenging treatment and in the efficiency of repair process. Influences of the occupational exposures and factors depending on genotypes or life style on cellular capacities are observed. Discussed results suggest that study in vitro with the challenging cells by radiation exposure and measuring, with the SCGE assay, the DNA damage before and after repair, may develop a good biomarker of the individual susceptibility to various genotoxins and exposures (environmental, occupational, therapeutic). Such a biomarker may have a potential use in a molecular epidemiology and preclinical identification.
Źródło:
Nukleonika; 2005, 50,suppl.2; 3-8
0029-5922
1508-5791
Pojawia się w:
Nukleonika
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Bacterial DNA repair genes and their eukaryotic homologues: 3. AlkB dioxygenase and Ada methyltransferase in the direct repair of alkylated DNA
Autorzy:
Nieminuszczy, Jadwiga
Grzesiuk, Elżbieta
Powiązania:
https://bibliotekanauki.pl/articles/1040921.pdf
Data publikacji:
2007
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
alkylating agents
adaptive response
AlkB
DNA repair
Opis:
Environmental and endogenous alkylating agents generate cytotoxic and mutagenic lesions in DNA. Exposure of prokaryotic cells to sublethal doses of DNA alkylating agents induces so called adaptive response (Ada response) involving the expression of a set of genes which allows the cells to tolerate the toxic and mutagenic action of such agents. The Ada response includes the expression of four genes: ada, alkA, alkB, and aidB. The product of ada gene, Ada protein, is an activator of transcription of all four genes. DNA bases damaged by alkylation are removed by distinct strategies. The most toxic lesion 3meA is removed by specific DNA glycosylase initiating base excising repair. The toxic and mutagenic O6meG is repaired directly by methyltransferases. 1meA and 3meC are corrected by AlkB DNA dioxygenase. The mechanisms of action of E. coli AlkB dioxygenase and its human homologs ABH2 and ABH3 are described in more details.
Źródło:
Acta Biochimica Polonica; 2007, 54, 3; 459-468
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Association of Polymorphism of Lys589glu Exo1 Gene with the Risk of Colorectal Cancer in the Polish Population
Autorzy:
Kabziński, Jacek
Przybylowska, Karolina
Mik, Michał
Sygut, Andrzej
Dziki, Łukasz
Dziki, Adam
Majsterek, Ireneusz
Powiązania:
https://bibliotekanauki.pl/articles/1395790.pdf
Data publikacji:
2014-08-01
Wydawca:
Index Copernicus International
Tematy:
colorectal cancer
polymorphisms
EXO1
DNA repair
Opis:
The incidence of colorectal cancer (CRC) is increasing from year to year. Despite intensive research CRC etiology remains unknown. Studies suggest that at the basis of the process of carcinogenesis can lie reduced efficiency of DNA repair mechanisms, often caused by polymorphisms in DNA repair genes. The aim of the study was to determine the relationship between gene polymorphism Lys589Glu of EXO1 gene and modulation of the risk of colorectal cancer in the Polish population. Determination of the molecular basis of carcinogenesis process and predicting increased risk will allow qualifying patients to increased risk group and including them in preventive program. Material and methods. The material used in study was blood collected from 130 patients diagnosed with colorectal cancer. The control group consisted of 135 healthy people. Genotyping was performed by TaqMan method. Results. The results obtained indicate that the genotype Lys/Glu is associated with an increased risk of colorectal cancer (OR 1.811, 95% Cl 1.031-3.181, p = 0.038). Conclusion. On the basis of these results, we conclude that Exo1 gene polymorphism Lys589Glu may be associated with an increased risk of colorectal cancer.
Źródło:
Polish Journal of Surgery; 2014, 86, 8; 370-373
0032-373X
2299-2847
Pojawia się w:
Polish Journal of Surgery
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
The Role of the XPF Gene Polymorphism (Xrcc4) Ser835ser in the Risk of Malignant Transformation of Cells in the Colorectal Cancer
Autorzy:
Kabziński, Jacek
Majsterek, Ireneusz
Dziki, Adam
Mik, Michał
Powiązania:
https://bibliotekanauki.pl/articles/1395528.pdf
Data publikacji:
2015-02-01
Wydawca:
Index Copernicus International
Tematy:
colorectal cancer
XRCC4
XPF
DNA repair
Opis:
Participation of DNA repair systems in the pathogenesis of cancer has been a suspected phenomenon for a long time. Decreased efficiency in DNA repair translates to their ability to fix and consequently leads to mutations and the process of carcinogenesis. Linking individual polymorphisms of DNA repair systems with an increased risk of colorectal cancer will allow the classification of patients to high-risk groups and their placement under preventive program. The aim of the study was to determine the effect of XPF gene polymorphism Ser835Ser on increasing the risk of colorectal cancer in the Polish population. Material and methods. as the material blood collected from 146 patients diagnosed with colon cancer was used. The control group consisted of 149 healthy subjects. Genotyping was performed by Taq- Man method. Results. The results indicate that genotype TCC/TCT is associated with an decreased risk of colorectal cancer (OR 0.574; CI 95% 0.335-0.984; p=0.043). Conclusions. Based on these results, we conclude that the XPF gene polymorphism Ser835Ser may be associated with a decreased risk of colorectal cancer
Źródło:
Polish Journal of Surgery; 2015, 87, 2; 83-85
0032-373X
2299-2847
Pojawia się w:
Polish Journal of Surgery
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Impaired base excision repair is related to the pathogenesis of non-alcoholic fatty liver disease
Autorzy:
Ziółkowska, Sylwia
Czarny, Piotr
Szemraj, Janusz
Powiązania:
https://bibliotekanauki.pl/articles/1024273.pdf
Data publikacji:
2020-12-30
Wydawca:
Uniwersytet Łódzki. Wydawnictwo Uniwersytetu Łódzkiego
Tematy:
DNA repair
non-alcoholic fatty liver
base excision repair
Opis:
Non-alcoholic fatty disease (NAFLD) is a liver disorder that affects up to 30% of the population, mainly in Western countries. It is estimated that up to 75% of NAFLD patients will develop a more aggressive form of the disease, non-alcoholic steatohepatitis (NASH). NAFLD can lead to fibrosis and liver failure; however, it is difficult to diagnose NAFLD due to its non-specific symptoms. Unfortunately, there is no treatment available for this disease. The risk factors of NAFLD are obesity and insulin resistance (IR). The molecular factors that seem to play an important role in the pathogenesis of NAFLD are oxidative stress as well as impaired DNA damage repair processes; a great body of evidence confirms an association with the base excision repair (BER) pathway. The activity of BER is decreased in patients with NAFLD and in animal models of this disease. In order to better understand the underlying basis of the disease, knowledge should be broadened in the area of DNA repair in NAFLD.
Źródło:
Acta Universitatis Lodziensis. Folia Biologica et Oecologica; 2020, 16; 5-11
1730-2366
2083-8484
Pojawia się w:
Acta Universitatis Lodziensis. Folia Biologica et Oecologica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Bacterial DNA repair genes and their eukaryotic homologues: 4. The role of nucleotide excision DNA repair (NER) system in mammalian cells
Autorzy:
Maddukuri, Leena
Dudzińska, Dominika
Tudek, Barbara
Powiązania:
https://bibliotekanauki.pl/articles/1040922.pdf
Data publikacji:
2007
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
trichothiodystrophy
Cockayne syndrome
xeroderma pigmentosum
DNA damage
DNA repair
nucleotide excision repair
Opis:
The eukaryotic cell encounters more than one million various kinds of DNA lesions per day. The nucleotide excision repair (NER) pathway is one of the most important repair mechanisms that removes a wide spectrum of different DNA lesions. NER operates through two sub pathways: global genome repair (GGR) and transcription-coupled repair (TCR). GGR repairs the DNA damage throughout the entire genome and is initiated by the HR23B/XPC complex, while the CSB protein-governed TCR process removes DNA lesions from the actively transcribed strand. The sequence of events and the role of particular NER proteins are currently being extensively discussed. NER proteins also participate in other cellular processes like replication, transcription, chromatin maintenance and protein turnover. Defects in NER underlay severe genetic disorders: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD).
Źródło:
Acta Biochimica Polonica; 2007, 54, 3; 469-482
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:
Hyperthermia can differentially modulate the repair of doxorubicin-damaged DNA in normal and cancer cells*.
Autorzy:
Blasiak, Janusz
Widera, Kinga
Pertyński, Tomasz
Powiązania:
https://bibliotekanauki.pl/articles/1043663.pdf
Data publikacji:
2003
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
hyperthermia
drug resistance
K562 cells
DNA repair
Opis:
Hyperthermia can modulate the action of many anticancer drugs, and DNA repair processes are temperature-dependent, but the character of this dependence in cancer and normal cells is largely unknown. This subject seems to be worth studying, because hyperthermia can assist cancer therapy. A 1-h incubation at 37°C of normal human peripheral blood lymphocytes and human myelogenous leukemia cell line K562 with 0.5 μM doxorubicin gave significant level of DNA damage as assessed by the alkaline comet assay. The cells were then incubated in doxorubicin-free repair medium at 37°C or 41°C. The lymphocytes incubated at 37°C needed about 60 min to remove completely the damage to their DNA, whereas at 41°C the time required for complete repair was shortened to 30 min. There was also a difference between the repair kinetics at 37°C and 41°C in cancer cells. Moreover, the kinetics were different in doxorubicin-sensitive and resistant cells. Therefore, hyperthermia may significantly affect the kinetics of DNA repair in drug-treated cells, but the magnitude of the effect may be different in normal and cancer cells. These features may be exploited in cancer chemotherapy to increase the effectiveness of the treatment and reduce unwanted effects of anticancer drugs in normal cells and fight DNA repair-based drug resistance of cancer cells.
Źródło:
Acta Biochimica Polonica; 2003, 50, 1; 191-195
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Soil bacterial community structure, metabolic adaptations, and their functional interactions to abiotic factors in Antarctica
Autorzy:
Jani, Kunal
Mahajan, Anoop
Kajale, Swapnil
Ashar, Aditee
Sharma, Avinash
Powiązania:
https://bibliotekanauki.pl/articles/16538455.pdf
Data publikacji:
2022
Wydawca:
Polska Akademia Nauk. Czasopisma i Monografie PAN
Tematy:
Antarctica
UV radiations
adaption strategies
extreme environments
DNA repair
Opis:
Antarctica features one of the most ancient, largest glacier reserves and the most pristine environment left on the earth. However, in the last few decades disturbances due to industrialization and release of greenhouse gases have led to serious consequences such asmelting of polar ice sheets, changing atmospheric chemistry and ozone depletion. Here, we use high-throughput sequencing to understand the impact of subtle changes in environmental parameters on bacterial communities. We observed dominance of Cyanobacteria (41.93%) followed by Bacteroidetes (14.8%), Acidobacteria (13.35%), Proteobacteria (9.67%), Actinobacteria (7.79%), Firmicutes (3.46%) among all the samples collected every alternate day for 20 days. Additionally, metagenomic imputations revealed a higher abundance of gene families associated with DNA repair and carotenoid biosynthesis enabling bacterial communities to resist and function under the high UV radiations. We further observed bacterial communities are dependent on the single carbon metabolism as a strategy for nutrient uptake in such nutrient deprived conditions.
Źródło:
Polish Polar Research; 2022, 43, 1; 21-36
0138-0338
2081-8262
Pojawia się w:
Polish Polar Research
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Bacterial DNA repair genes and their eukaryotic homologues: 5. The role of recombination in DNA repair and genome stability
Autorzy:
Nowosielska, Anetta
Powiązania:
https://bibliotekanauki.pl/articles/1040931.pdf
Data publikacji:
2007
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
homologous recombination
Escherichia coli
DSB
replication forks
DNA repair
Opis:
Recombinational repair is a well conserved DNA repair mechanism present in all living organisms. Repair by homologous recombination is generally accurate as it uses undamaged homologous DNA molecule as a repair template. In Escherichia coli homologous recombination repairs both the double-strand breaks and single-strand gaps in DNA. DNA double-strand breaks (DSB) can be induced upon exposure to exogenous sources such as ionizing radiation or endogenous DNA-damaging agents including reactive oxygen species (ROS) as well as during natural biological processes like conjugation. However, the bulk of double strand breaks are formed during replication fork collapse encountering an unrepaired single strand gap in DNA. Under such circumstances DNA replication on the damaged template can be resumed only if supported by homologous recombination. This functional cooperation of homologous recombination with replication machinery enables successful completion of genome duplication and faithful transmission of genetic material to a daughter cell. In eukaryotes, homologous recombination is also involved in essential biological processes such as preservation of genome integrity, DNA damage checkpoint activation, DNA damage repair, DNA replication, mating type switching, transposition, immune system development and meiosis. When unregulated, recombination can lead to genome instability and carcinogenesis.
Źródło:
Acta Biochimica Polonica; 2007, 54, 3; 483-494
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
A comparison of the in vitro genotoxicity of anticancer drugs idarubicin and mitoxantrone.
Autorzy:
Błasiak, Janusz
Gloc, Ewa
Warszawski, Mariusz
Powiązania:
https://bibliotekanauki.pl/articles/1043821.pdf
Data publikacji:
2002
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
mitoxantrone
oxidative DNA damage
DNA damage
idarubicin
comet assay
DNA methylation
DNA repair
Opis:
Idarubicin is an anthracycline antibiotic used in cancer therapy. Mitoxantrone is an anthracycline analog with presumed better antineoplastic activity and lesser toxicity. Using the alkaline comet assay we showed that the drugs at 0.01-10 μM induced DNA damage in normal human lymphocytes. The effect induced by idarubicin was more pronounced than by mitoxantrone (P < 0.001). The cells treated with mitoxantrone at 1 μM were able to repair damage to their DNA within a 30-min incubation, whereas the lymphocytes exposed to idarubicin needed 180 min. Since anthracyclines are known to produce free radicals, we checked whether reactive oxygen species might be involved in the observed DNA damage. Catalase, an enzyme inactivating hydrogen peroxide, decreased the extent of DNA damage induced by idarubicin, but did not affect the extent evoked by mitoxantrone. Lymphocytes exposed to the drugs and treated with endonuclease III or formamidopyrimidine-DNA glycosylase (Fpg), enzymes recognizing and nicking oxidized bases, displayed a higher level of DNA damage than the untreated ones. 3-Methyladenine-DNA glycosylase II (AlkA), an enzyme recognizing and nicking mainly methylated bases in DNA, increased the extent of DNA damage caused by idarubicin, but not that induced by mitoxantrone. Our results indicate that the induction of secondary malignancies should be taken into account as side effects of the two drugs. Direct strand breaks, oxidation and methylation of the DNA bases can underlie the DNA-damaging effect of idarubicin, whereas mitoxantrone can induce strand breaks and modification of the bases, including oxidation. The observed in normal lymphocytes much lesser genotoxicity of mitoxantrone compared to idarubicin should be taken into account in planning chemotherapeutic strategies.
Źródło:
Acta Biochimica Polonica; 2002, 49, 1; 145-155
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
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