In Vivo Study of Chromosomal Instability in Lymphocytes of Radiotherapy Patients (original) (raw)
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International Journal of Radiation Research
Background: There is not yet an appropriate biomarker to predict or follow radiosensitivity of Breast cancer (BC) patients during or after radiotherapy. The aim of this study was to monitor chromosomal aberrations (CA) induced before and during radiotherapy in peripheral blood lymphocytes of BC patients. Materials and Methods: Age-matched twenty normal healthy individuals and 20 invasive ductal BC patients were enrolled in this study. A blood sample was obtained from normal healthy women and BC patients before and after the first, two and four weeks after radiotherapy. Lymphocyte microculture was initiated in 4.5ml complete RPMI-1640 medium. Cells were harvested 50 hours after culture initiation. Cells were harvested based on standard protocols. Hundreds of well-spread mitoses were scored under a light microscope with a magnification of x1000 for various types of CA. Data were statistically analyzed and p<0.05 was considered a significant difference. Results: Results indicated a higher frequency of CA in lymphocytes of un-irradiated BC patients compared to healthy normal individuals, although not statistically significant (p>0.05). High frequencies of CA were observed in lymphocytes of BC patients after radiotherapy, significantly different from the un-irradiated group (p<0.01). The increase in the frequency of CA was increased with increasing radiation dose. Conclusion: Genome instability may contribute to high background and radiationinduced CA in lymphocytes of BC patients. However, there is also the possibility of a radio-adaptation of cells during the course of radiotherapy. Results imply that dicentric chromosomes might be valuable cytogenetic bioindicators to monitor the response of BC patients to radiotherapy.
Chromosomal aberrations induced by radiotherapy in lymphocytes from patients with lung cancer
Journal of Environmental Biology, 2009
In this study we tried to define incidence and types of chromosomal aberrations (CAs) caused by radiotherapy (RT) in circulating lymphocytes from patients with lung cancer. For this purpose, we used cumulative dose-effect relationship, and correlate these data with statistical parameters. CAs were evaluated in terms of chromosome break, dicentric, ring and chromosome gap. Abnormal metaphase number (AMN) was also calculated. Chromosome studies were carried out in peripheral blood lymphocytes of 20 cancer patients receiving RT. Patients were treated with 10 Gy of gamma (γ) radiation during five wk(s). In all patients, a significant increase in AMN and frequency of CAs (e.g. chromosome break, dicentric, ring and chromosome gap) observed during the RT depend on cumulative radiation dose when compared to before RT, and this increase was statistically significant (p<0.05). The highest CAs frequency was observed at the end of fifth wk. Among the CAs, chromosome breaks have a high incidence. But no CAs and abnormal metaphase was observed in lymphocytes before RT. The present study showed that RT possess a significant effect in increasing of CAs and chromosome break, dicentric, ring and chromosome gap are very sensitive and useful biomarkers in the study of this effect. In other words, these CAs may be used as possible fingerprints of RT.
Cytogenetic effects of radiotherapy: Frequency and types of chromosome aberrations
International Journal of Radiation Oncology Biology Physics, 1990
The frequency and types of chromosome aberrations induced by ionizing radiation in cancer patients were evaluated in 24 cases studied just before and immediately after radiotherapy. The incidence of aberrant metaphases prior to treatment was 9.913% and increased significantly after treatment to 32.8%. The frequency of chromosome aberrations before radiotherapy was, with the exception of the cases of breast cancer and seminoma, significantly higher than that in our laboratory controls. A comparison of chromosome abnormalities observed before and after treatment indicated that dicentric translocations, rings, and reciprocal translocations increased by a factor of 23, 13, and 11, respectively, after radiotherapy. Ionizing radiation produces more asymmetrical than symmetrical chromosome aberrations and mlore two-break than one-break anomalies.
Clinical Biochemistry, 2011
Objective: Studies indicate that ionizing radiation can induce persistent genetic instability in a high proportion of exposed cells. It has also been reported that exposure of radiotherapy workers to ionizing radiation causes chromosomal damages. Some of the damaged cells show a large number of aberrations such as dicentrics, polycentrics, rings, and numerous acentric fragments.To determine, whether chromosomal damages can be used as a biomarker of possible radiation in occupational exposure in a hospital setting. Methodology: In this study, chromosome abnormalities were evaluated in peripheral blood lymphocytes from fifty medical radiotherapy workers who handled ionizing radiation for an average of twelve years, and forty three control individuals who did not knowingly come in contact with any radiation source. Chromosome aberrations were evaluated by the conventional solid stain technique. Results: Dicentrics, fragments, followed by ring chromosomes, as well as total chromosome aberrations were elevated in the experimental group. We did not observe any aneuploidy chromosome in the present study. Although the level of exposure was below the annual permissible limit of twenty mSv/y recommended by the International Commission for Radiation Protection for whole body exposure, the mean frequencies of different chromosomal aberrations were higher in radiotherapy workers compared with controls (P=0.041). Although the mean frequencies of chromosomal aberrations in the female workers (3.5±1.42) was slightly higher than in males (3.28±0.95), there was no significant differences (P=0.74) in the frequency of chromosome aberration between males and females of ionizing radiotherapy workers.
Cytogenetic effects of radiotherapy. Breakpoint distribution in induced chromosome aberrations
Cancer Genetics and Cytogenetics, 1989
A total of 660 breakpoints were identified in the chromosome aberrations detected in lymphocytes from cancer patients after radiotherapy. The results show that chromosomes 1, 3, and 7 were significantly more affected than other chromosomes by ionizing radiation in viva. Chromosome arms lp, lq, 7q, and 11p were also significantly mare affected. Some bands also showed a special sensitivity to radiation, and band lq32 was the most affected. This band is proposed as a "hot paint" for the clastagenic effect of ionizing radiation. A significant cluster-•ng of breakpoints in G bands was also found, especially at the telomeres, as previously described by other authors. Clustering of breakpaints was also observed in bands where fragile sites, protaoncogenes, breakpoints involved in chromosomal cancer rearrangements, and breakpoints involved in chromosomal evolution of the Hominaidea are located.
International Journal of Radiation Oncology*Biology*Physics, 2002
Purpose: Stable chromosomal aberrations (SCAs) have been found in circulating lymphocytes from patients treated for breast carcinoma. Therefore, we tried to define their incidence in such patients, to determine an in vitro dose-effect relationship, and to correlate these data with clinical parameters. Methods and Materials: This prospective study included 25 patients who, after surgery, underwent either radiotherapy (RT) alone (n ؍ 15) or RT combined with chemotherapy (n ؍ 10). SCAs were scored using the fluorescent in situ hybridization technique before RT and 4 and 12 months after RT. Dose-effect curves were established by in vitro irradiation of blood samples with 2 and 4 Gy, before and after treatment. Results: In all patients, the rate of SCAs increased significantly after external irradiation. No significant decrease in SCAs was observed during the first year after RT. RT and chemotherapy had no effect on the lymphocyte in vitro dose-effect relationship. No relationship was found in the distribution of patients between the yield of SCAs scored after external irradiation and after in vitro irradiation. SCAs after RT or in vitro irradiation did not correlate with family history of breast carcinoma or acute toxicity of treatment. More significantly, the yield of SCA after external irradiation was strongly related to the irradiation of the internal mammary chain and the supraclavicular lymph node area, suggesting that the volume of irradiated blood vessels was an essential parameter in determining the rate of SCAs. Conclusion: A high and stable yield of SCAs persisted at least 1 year after external irradiation. The nature of the volume irradiated containing large blood vessels was the major determinant of the observed biologic dose.
Radiation and Environmental Biophysics, 2010
The aim of the study was to compare the spontaneous and ex vivo radiation-induced chromosomal damage in lymphocytes of untreated prostate cancer patients and age-matched healthy donors, and to evaluate the chromosomal damage, induced by radiotherapy, and its persistence. Blood samples from 102 prostate cancer patients were obtained before radiotherapy to investigate the excess acentric fragments and dicentric chromosomes. In addition, in a subgroup of ten patients, simple exchanges in chromosomes 2 and 4 were evaluated by fluorescent in situ hybridization (FISH), before the onset of therapy, in the middle and at the end of therapy, and 1 year later. Data were compared to blood samples from ten age-matched healthy donors. We found that spontaneous yields of acentric chromosome fragments and simple exchanges were significantly increased in lymphocytes of patients before onset of therapy, indicating chromosomal instability in these patients. Ex vivo radiation-induced aberrations were not significantly increased, indicating proficient repair of radiation-induced DNA double-strand breaks in lymphocytes of these patients. As expected, the yields of dicentric and acentric chromosomes, and the partial yields of simple exchanges, were increased after the onset of therapy. Surprisingly, yields after 1 year were comparable to those directly after radiotherapy, indicating persistence of chromosomal instability over this time. Our results indicate that prostate cancer patients are characterized by increased spontaneous chromosomal instability. This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks. Radiotherapy-induced chromosomal damage persists 1 year after treatment.
Chromosomal instability in in vivo radiation exposed subjects
International Journal of Radiation Biology, 1998
asymmetric exchanges usually lead to proliferative Purpose: To investigate whether delayed chromosomal instability cell death in the subsequent mitoses and mainly arises in human peripheral T lymphocytes exposed in vivo to c-
Scientific reports, 2017
The mechanisms behind the transmission of chromosomal aberrations (CA) remain unclear, despite a large body of work and major technological advances in chromosome identification. We reevaluated the transmission of CA to second- and third-division cells by telomere and centromere (TC) staining followed by M-FISH. We scored CA in lymphocytes of healthy donors after in vitro irradiation and those of cancer patients treated by radiation therapy more than 12 years before. Our data demonstrate, for the first time, that dicentric chromosomes (DCs) decreased by approximately 50% per division. DCs with two centromeres in close proximity were more efficiently transmitted, representing 70% of persistent DCs in ≥M3 cells. Only 1/3 of acentric chromosomes (ACs), ACs with four telomeres, and interstitial ACs, were paired in M2 cells and associated with specific DCs configurations. In lymphocytes of cancer patients, 82% of detected DCs were characterized by these specific configurations. Our findi...
International Journal of Radiation Oncology*Biology*Physics, 2003
Purpose: To measure chromosomal aberrations in blood lymphocytes from breast cancer patients treated with radiotherapy after quadrantectomy or tumorectomy. Methods and Materials: Twenty-two breast cancer patients treated with breast-conserving surgery and radiation were evaluated. Adjuvant chemotherapy was also given to 9 patients. Blood samples were obtained before radiotherapy, after about one-half of the fractions, and at the end of the treatment of the whole breast (50 Gy). Chromosome aberrations in peripheral blood lymphocytes were measured using chemical-induced premature chromosome condensation combined with fluorescence in situ hybridization. Results: Radiation treatment produced a significant increase in the yield of chromosomal aberrations. A large interindividual variability was observed. The variability was not related to field size, previous chemotherapy, or treatment morbidity. Chromosome aberrations in lymphocytes at the end of the treatment were significantly higher in the group of patients with no lymph nodes surgically removed before the treatment than in the group of patients with more than 10 lymph nodes removed. Conclusions: The number of lymph nodes within the radiation field is an important factor affecting the yield of radiation-induced chromosomal aberrations in breast cancer patients.