Micronucleus incidence and their chromosomal origin related to therapy in acute lymphoblastic leukemia (ALL) patients: Detection by micronucleus and FISH techniques

Acar, Hasan; Çalışkan, Ümran; Demirel, Sennur; Largaespada, David A.

doi:10.1002/tcm.1022

Cited by 24 publications

(9 citation statements)

References 22 publications

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“…Also, the gastric normal tissue in this patient was analysed separately and when compared to the gastric normal tissue from the other patients in this study, chromosomal abnormalities were higher. This may possibly suggest induced aneuploidy by the chemotherapy treatment, as has been shown in other studies (Acar et al, 2001;Kamiguchi and Tateno, 2002;Silva et al, 2002;Frias et al, 2003), but numbers are obviously too small to confirm this. Furthermore, in several cases, multiple brushes were taken from the same tumour to study intratumoural heterogeneity.…”

Section: Resultsmentioning

confidence: 63%

Fluorescence in situ hybridisation analysis of chromosomal aberrations in gastric tissue: the potential involvement of Helicobacter pylori

et al. 2005

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In this series of experiments, a novel protocol was developed whereby gastric cells were collected using endoscopic cytology brush techniques, and prepared, such that interphase fluorescence in situ hybridization (FISH) could be performed. In total, 80 distinct histological samples from 37 patients were studied using four chromosome probes (over 32 000 cells analysed). Studies have previously identified abnormalities of these four chromosomes in upper GI tumours. Using premalignant tissues, we aimed to determine how early in Correa's pathway to gastric cancer these chromosome abnormalities occurred. Aneuploidy of chromosomes 4, 8, 20 and 17(p53) was detected in histologically normal gastric mucosa, as well as in gastritis, intestinal metaplasia, dysplasia and cancer samples. The levels of aneuploidy increased as disease severity increased. Amplification of chromosome 4 and chromosome 20, and deletion of chromosome 17(p53) were the more common findings. Hence, a role for these abnormalities may exist in the initiation of, and the progression to, gastric cancer. Helicobactor pylori infection was determined in premalignant tissue using histological analysis and PCR technology. Detection rates were comparable. PCR was used to subtype H. pylori for CagA status. The amplification of chromosome 4 in gastric tissue was significantly more prevalent in H. pylori-positive patients (n ¼ 7) compared to H. pylori-negative patients (n ¼ 11), possibly reflecting a role for chromosome 4 amplification in H. pylori-induced gastric cancer. The more virulent CagA strain of H. pylori was associated with increased disease pathology and chromosomal abnormalities, although numbers were small (CagA þ n ¼ 3, CagAÀ n ¼ 4). Finally, in vitro work demonstrated that the aneuploidy induced in a human cell line after exposure to the reactive oxygen species (ROS) hydrogen peroxide was similar to that already shown in the gastric cancer pathway, and may further strengthen the hypothesis that H. pylori causes gastric cancer progression via an ROS-mediated mechanism.

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Section: Resultsmentioning

confidence: 63%

Fluorescence in situ hybridisation analysis of chromosomal aberrations in gastric tissue: the potential involvement of Helicobacter pylori

et al. 2005

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“…The presence of telomere signals in micronuclei might have been the result of telomere breakage and/or dysfunctional telomeres in the lymphocytes of breast cancer patients. There was an attempt made by Acar et al [33] to find the chromosomal origin in FISH on MN in acute lymphoblastoid leukaemia patients but they did not report telomere damage pattern. In another work Norppa et al [34] tried to find the contents of human micronuclei and reported telomeric signals in some MN population.…”

Section: Resultsmentioning

confidence: 97%

Analysis of telomere damage by fluorescence in situ hybridisation on micronuclei in lymphocytes of breast carcinoma patients after radiotherapy

Banerjee

Sharma

Hegde

et al. 2007

Breast Cancer Res Treat

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Radiotherapy has become an indispensable tool in the effective management of most of the cancers. There have been efforts earlier to study the differential radio-sensitivity patterns in patients undergoing radiation treatment to correlate with treatment induced complications such as tissue injury, cell death, and chromosomal aberration frequencies etc. The present study is an attempt to correlate the radiation-induced damage in the peripheral blood lymphocytes (PBLs) of breast cancer patients with the frequency of telomere mediated chromosomal damage. Blood samples from 55 patients with (Gr-II and Gr-III) CA-breast were obtained pre- and post-radiotherapy. The patients were treated with external beam radiotherapy of 50.4 Gy over a period of 6 weeks. Chromosome damage was measured by analysing micronucleus (MN) frequency in PBLs. The MN-frequency of the irradiated patients increased significantly compared to the patients being self-controls. The micronuclei were hybridized with telomere probes to study the extent of telomere damage. The fluorescence signals of the telomere regions in the first generation of the binucleated cells were significantly higher in the post-radiotherapy patients. There was also significant correlation observed in the patients with higher-grade tumours. Inter-individual variability was observed in the radiation-induced MN frequency in lymphocytes of patients after six weeks of radiotherapy. There was a significant correlation between functionally intact telomeres and the cellular response to ionising radiation. Our findings suggest that fluorescence in situ hybridisation on micronuclei could be effectively used as routine clinical application to determine the individual sensitivity to ionising radiation with respect to telomere damage.

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“…In this context, chemotherapy plays a key role in the treatment of many neoplasias, improving the prognosis of cancer patients, especially children [1]. However, it is well known that some cytostatic drugs can induce DNA damage in both somatic and germ cells, either increasing the incidence of a second malignancy [2] or the incidence of primary tumour in the offspring, when administered in the reproductive age [3][4][5]. In fact, increasing numbers of patients with second malignancies have recently been observed among long survivors of paediatric cancer [6,7].…”

Section: Introductionmentioning

confidence: 99%

DNA damage in lymphocytes and buccal mucosa cells of children with malignant tumours undergoing chemotherapy

et al. 2008

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The aim of the present study was to evaluate DNA damage (micronucleus) in cytokinesis-blocked lymphocytes and exfoliated buccal mucosa cells from children with malignant tumours and under chemotherapy. Micronucleated cells (MNCs) were assessed from children before and during chemotherapy. A total of 21 healthy children (controls), matched for gender and age, were used as control. The results pointed out higher frequencies of micronucleated lymphocytes in children with malignant tumour before any therapy when compared to healthy probands. Furthermore an increase of micronucleated lymphocytes during chemotherapy was detected when compared to the data obtained before chemotherapy. No statistically significant increases of MNCs were noticed in buccal mucosa cells at any of the timepoints evaluated. Taken together, these data indicate that the presence of malignant tumours may increase the frequency of DNA damage in circulating lymphocytes, these cells being more sensitive for detecting chromosome aberrations caused by anti-cancer drugs.

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Micronucleus incidence and their chromosomal origin related to therapy in acute lymphoblastic leukemia (ALL) patients: Detection by micronucleus and FISH techniques

Cited by 24 publications

References 22 publications

Fluorescence in situ hybridisation analysis of chromosomal aberrations in gastric tissue: the potential involvement of Helicobacter pylori

Fluorescence in situ hybridisation analysis of chromosomal aberrations in gastric tissue: the potential involvement of Helicobacter pylori

Analysis of telomere damage by fluorescence in situ hybridisation on micronuclei in lymphocytes of breast carcinoma patients after radiotherapy

DNA damage in lymphocytes and buccal mucosa cells of children with malignant tumours undergoing chemotherapy

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