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DNA damage repair and genetic polymorphisms: assessment of individual sensitivity and repair capacity
No full textPurpose: To study the repair capacity after X-ray irradiation in human peripheral blood cells of healthy subjects, in relation to their genotypes.
Methods and Materials: The peripheral blood of 50 healthy subjects was irradiated in vitro with 2Gy of X rays and the induced DNA damage was measured by Comet assay immediately after irradiation. DNA repair was detected by analyzing the cells at defined time intervals after the exposure. Furthermore, all subjects were genotyped for XRCC1, OGG1, and XPC genes.
Results: After X-ray irradiation, persons bearing XRCC1 homozygous variant (codon 399) genotype exhibited significantly lower Tail DNA values than those bearing wild-type and heterozygous genotypes. These results are also confirmed at 30 and 60 min after irradiation. Furthermore, XPC heterozygous subjects (variant codon 939) showed lower residual DNA damage 60 min after irradiation compared with wild-type and homozygous genotypes.
Conclusion: The results of the present study show that polymorphisms in DNA repair genes could influence individual DNA repair capacity. (c) 2006 Elsevier Inc
Astrocytoma gap junction intercellular communication (GJIC) is modulated by X-ray activated microglia
No full textResveratrol induces DNA double strand breaks through human Topoisomerase II interaction
No full textResveratrol, a stilbene found in grapes and wine, is one of the most interesting natural
compound due to its role exerted in cancer prevention and therapy. In particular, resveratrol
is able to delay cell cycle progression and to induce apoptotic death in several cell lines.
Here we report that resveratrol treatment of human glioblastoma cells induces a delay in
cell cycle progression during S phase associated with an increase in histone H2AX phosphorylation.
Furthermore, with an in vitro assay of topoisomerase IIa catalytic activity
we show that resveratrol is able to inhibit the ability of recombinant human TOPO IIa to
decatenate kDNA, so that it could be considered a TOPO II poison
Resveratrol affects X-ray induced apoptosis and cell cycle delay in human cells in vitro
No full textMany studies in human and mammalian cells have shown the involvement of resveratrol in the modulation of several biological processes, including the regulation of carcinogenesis, However, the molecular mechanisms underlying its antitumorigenic activity are still not defined. There is great interest in developing new agents that can modify the efficacy of radiation therapy. The aim of the present study was to investigate the cellular response to treatments with X rays and resveratrol, alone or in combination, in terms of DNA damage, cell cycle delays and induction of apoptosis. Lymphoblastoid cells AHH-1 were treated and analysed at successive sampling times in order to study the induct on of DNA breaks using the Comet assay and the induction of apoptosis and cell cycle modulation through cytofluorimetric analysis. Our results suggest that resveratrol causes the induction of apoptosis and a block of cell cycle progression at an early step of S-phase. Furthermore, resveratrol mitigates the apoptotic clearance of irradiated cells and prevents the G(2) phase cell cycle arrest induced by X-rays
Recent advances in pharmacological therapy of Parkinson's disease: levodopa and carbidopa protective effects against DNA oxidative damage
No full text
Influence of glutathione S-transferase polymorphisms on genotoxic effect induced by tobacco smoke
No full textGenotoxicity of tobacco smoke has long been investigated and tobacco smoke is considered to be one of the principal human carcinogens. Although its role in DNA-damage induction and cancer development has been documented, the mechanisms by which this happens are not well understood. Many chemical constituents of tobacco smoke are enzymatically metabolized by phase-I and phase-II enzymes, but modifications in coding and regulating sequences of these genes could influence their ability to detoxify these compounds.
In this work, we studied several enzymes involved in the metabolism of xenobiotics, viz. the glutathione S-transferases (GST) M1, T1, P1 and A1, with respect to their influence on the genotoxic effects induced by cigarette smoking. We assessed the genotoxic effects of tobacco smoke on peripheral blood lymphocytes of 72 healthy caucasians by use of the chromosomal aberration (CA) assay and the micronucleus (MN) test.
Genotypes of GST M1, T1, P1 and A1 were determined by means of the polymerase chain reaction and methods based on restriction fragment length polymorphism (RFLP).
We found that smoke and gender are the two variables that most influence the DNA damage. In particular, we observed that female smokers seem to be more sensitive than male, smokers, having a significantly higher frequency of CAs. Moreover, a significant increase in frequency of micronuclei in bi-nucleated cells (BNMN) was found in smokers, but not in non-smokers. This increase seems to be influenced not only by age and gender, but also by genetic constitution. Subjects carrying GSTM1-null genotype seemed to have an higher susceptibility to DNA damage induced by tobacco smoke than GSTM1-positive ones. When considering a combination of GST genotypes, we found a lower BNMN frequency in subjects with GSTP1 variant allele plus GSTM1-positive genotypes, while the most damaged cells are found in subjects bearing GSTM1-null plus GSTP1-wild type. Our results suggest that investigation of the association between several gene polymorphisms and important endpoints of DNA damage could contribute to better understanding the role of gene-gene interactio
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