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1

Relation betwwn DNA replication and DNA repair in human lymphocytes proliferating in vitro in the presence and in absence of mutagen

100%

Szyfter K., Wiktorowicz K., Wielgosz M. S., Zajaczek S., Kujawski M., Jaloszynski P., Czub M., Markowska M.

Journal of Applied Genetics

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1995

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vol. 36

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issue 4

379-388

EN

The effects of mutagens on DNA replication and DNA repair were studied in peripheral blood lymphocytes (BPL) obtained 21 healthy subjects, 2 samples from healthy heterozygote of Xeroderma pigmentosum (XP) and 2 samples from patient with clinically recognized XP.Inter-individual variations were found in DNA replication and in the level of spontanous DNA repair measured under standard culture condition.Exposure of human PBL proliferating in vitro to B(a)P was followed by a partial inhibition of replicative DNA synthesis in all subjects and by induction of DNA repair in healthy subjects.In XP patients DNA repair sythesis remained at the level attributed to spontaneous DNA repair.The response to mutagen varied individually.Results were analysed statistically.It was established that the studied indices of DNA synthesis correlete well with each other.The highest correlation was found between the levels of spontaneous and B(a)P-induced DNA repair.It is concluded that the level of spontaneous DNA repair is predictive for an estimation of cells ability to repair DNA damage.Inter-individual variations in the inhibition of DNA replication and in DNA repair sythesis are also dependet on the type of mutagen as shown by effect of other mutagens.Different effects of mutagen exposure on the inhibition of DNA replicative sythesis and induction of DNA repair can be explained by genetically controlled differences in the activity of enzymes responsible for mutagen processing and lesion removal.

2

Documenting ancient DNA quality via alpha satellite amplification and assessment of clone sequence diversity

88%

Pusch C. M., Kayademir T., Prangenberg K., Conard N. J., Czarnetzki A., Blin N.

Journal of Applied Genetics

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2002

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vol. 43

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issue 3

351-363

EN

C/GT/A nucleotide alterations have been shown to hamper the straightforward interpretation of mitochondrial DNA sequence data derived from ancient tissues. Attempting to characterise this finding with respect to nuclear DNA, we contrasted two established protocols: (i) an enzymatic repair of damaged DNA, thereby translating and closing nicks in the DNA, and (ii) the application of N-phenacylthiazolium bromide, which cleaves glucose-derived protein crosslinks, presumably derived from Maillard reactions. We used medieval human bones that were refractory to standard PCR procedures. Due to negligible presence of short tandem repeat loci and also mitochondrial sequences, the extracted ancient DNA needed a higher copy PCR system to yield amplification products. The chosen PCR target was specific alphoid repetitive DNA with an experimentally determined minimum of 1000 copies per haploid genome. Alphoid repeat segments were generated from both contemporary DNA and DNA extracts of two human skeletons dating from 450-600 AD (omitting uracil N-glycosylase pre-treatment of the extracted samples), and were subsequently cloned and sequenced. The sequences were evaluated for the number and type of nucleotide alterations noted after the different pre-treatments, and were compared to our alphoid consensus sequence generated from modern DNA. Both methods failed to reflect the expected 32% variability among single alphoid repeats (accounting for locus-specific differences and polymerase errors) as well as to display the actual 2.88 ratio of transitions to transversions. Our data obtained from high-copy-number nuclear DNA mirror the phenomenon of sequence deviations observed in mitochondrial DNA extracted from old specimens.

3

Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population

75%

Jelonek K., Gdowicz-Klosok A., Pietrowska M., Borkowska M., Korfanty J., Rzeszowska-Wolny J., Widlak P.

Journal of Applied Genetics

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2010

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vol. 51

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issue 3

343-352

EN

Single-nucleotide polymorphisms in genes involved in DNA-damage-induced responses are reported frequently to be a risk factor in various cancer types. Here we analysed polymorphisms in 5 genes involved in DNA repair (XPD Asp312Asn and Lys751Gln, XRCC1 Arg399Gln, APE1 Asp148Glu, NBS1 Glu185Gln, and XPA G-4A) and in a gene involved in regulation of the cell-cycle (CCND1 A870G). We compared their frequencies in groups of colon, head and neck, and breast cancer patients, and 2 healthy control groups: (1) matched healthy Polish individuals and (2) a NCBI database control group. Highly significant differences in the distribution of genotypes of the APE1, XRCC1 and CCND1 genes were found between colon cancer patients and healthy individuals. The 148Asp APE1 allele and the 399Gln XRCC1 allele apparently increased the risk of colon cancer (OR = 1.9-2.3 and OR = 1.5-2.1, respectively). Additionally, frequencies of XPD genotypes differed between healthy controls and patients with colon or head and neck cancer. Importantly, no differences in the distribution of these polymorphisms were found between healthy controls and breast cancer patients. The data clearly indicate that the risk of colon cancer is associated with single-nucleotide polymorphism in genes involved in base-excision repair and DNA-damage-induced responses.

4

Opposite responses in two DNA repair capacity tests in lymphocytes of head and neck cancer patients

75%

Sasiadek M., Schlade-Bartusiak K., Zych M., Noga L., Czemarmazowicz H.

Journal of Applied Genetics

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2002

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vol. 43

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issue 4

525-534

EN

Genomic instability has long been recognized as the main feature of neoplasia and a factor modulating individual cancer susceptibility. There are attempts to find effective assays of both individual DNA repair capacity and genetic instability, and their relation to the cancer risk. Genetic predisposition plays an important role in the etiology and development of head and neck squamous cell carcinoma (HNSCC). The aim of our study was to search for a correlation between chromosomal instability and DNA repair capacity in HNSCC patients and healthy controls. The chromosomal instability was measured by the number of bleomycin (BLM)-induced chromosomal aberrations and diepoxybutane (DEB)-induced sister chromatid exchanges. The DNA repair capacity was assessed using the DEB-induced adaptive response (AR). The HNSCC patients in our study showed a significant increase in chromosomal instability after a preterminal exposure of their lymphocytes to either BLM for the last 5 h or DEB for the last 24 h of incubation. However, the AR was higher in HNSCC patients than in the control group, suggesting an increase in the DNA repair capacity in the cancer patients as compared to the control. There is no correlation between the DNA repair capacity estimated on the basis of preterminal exposures to BLM and DEB and the DNA repair capacity estimated on the basis of the adaptive response to DEB. The preterminal exposure and the adaptive response test may activate different DNA repair mechanisms.

5

DNA damage and repair after exposure to sevoflurane in vivo, evaluated in Swiss albino mice by the alkaline comet assay and micronucleus test

75%

Brozovic G., Orsolic N., Rozgaj R., Kasuba V., Knezevic F., Knezevic A. H., Benkovic V., Lisicic D., Borojevic N., Dikic D.

Journal of Applied Genetics

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2010

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vol. 51

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issue 1

79-86

EN

The relationship between DNA damage and repair of peripheral blood leukocytes, liver, kidney and brain cells was investigated in Swiss albino mice (Mus musculus L.) after exposure to sevoflurane (2.4 vol% for 2 h daily, for 3 days). Genetic damage of mouse cells was investigated by the comet assay and micronucleus test. To perform the comet assay, mice were divided into a control group and 4 groups of exposed mice sacrificed on day 3 of the experiment, at 0, 2, 6 or 24 h after the last exposure to sevoflurane. Mean tail length (TL), tail moment (TM), and tail intensity (TI) values were significantly higher in exposed mice (all examined organs) than in the control group. Significant DNA damage immediately after exposure to sevoflurane was observed in leukocytes. Damage induction in the liver, kidney, and brain occurred 6 h later than in leukocytes, as expected according to the toxicokinetics of the drug, where blood is the first compartment to absorb sevoflurane. However, none of the tested tissues revealed signs of repair until 24 h after the exposure. To distinguish the unrepaired genome damage in vivo, the micronucleus test was applied. Number of micronuclei in reticulocytes showed a statistically significant increase, as compared with the control group at all observed times after the treatment.

6

Aneuploidy, chromosomal missegregation, and cell cycle reentry in Alzheimer's disease

63%

Zekanowski C., Wojda U.

Acta Neurobiologiae Experimentalis

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2009

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vol. 69

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issue 2

232-253

EN

Alzheimer's disease (AD) is a neurodegenerative disorder with a complex etiology and pathogenesis. Chromosome missegregation was proposed two decades ago to be responsible for neurodegeneration in AD patients. It was speculated that the aneuploidy is a result of aberrant cell cycle of neuronal progenitors during adult neurogenesis and/or of mature neurons. There is mounting evidence of increased rate of general aneuploidy and cell cycle reentry in the AD patients' brains, with area-specific pattern. In this review, we discuss the involvement of chromosome instability, genome damage and cell cycle impairment in AD pathology.

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Relation betwwn DNA replication and DNA repair in human lymphocytes proliferating in vitro in the presence and in absence of mutagen

Documenting ancient DNA quality via alpha satellite amplification and assessment of clone sequence diversity

Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population

Opposite responses in two DNA repair capacity tests in lymphocytes of head and neck cancer patients

DNA damage and repair after exposure to sevoflurane in vivo, evaluated in Swiss albino mice by the alkaline comet assay and micronucleus test

Aneuploidy, chromosomal missegregation, and cell cycle reentry in Alzheimer's disease