The Cytogenetic Effects on Peripheral Blood Lymphocytes in Cancer Patients After Radiation Therapy: Chromosome Aberrations and Micronuclei (original) (raw)
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Persistence of Micronuclei in Lymphocytes of Cancer Patients after Radiotherapy
Radiation Research, 2002
To verify the applicability of the micronucleus (MN) yield in peripheral blood lymphocytes (PBLs) as a quantitative biodosimeter for monitoring in vivo ionizing radiation damage, we applied the cytokinesis-blocked micronucleus assay in PBLs of cancer patients treated with partial-body radiotherapy. Dosimetric information on these 13 patients represented a wide range in the number of fractions, cumulative tumor dose, total integral dose, and equivalent total-body absorbed dose. We found in PBLs of these patients that (1) the MN yield increased linearly with the equivalent total-body absorbed dose (r ؍ 0.8, P ؍ 0.002), (2) the distributions of the MN yields deviated significantly from Poisson, and (3) there was a general decline in MN yields with increasing length of follow-up, but with considerable variation between individuals. The average rate of decline was found to be linear and was correlated with the equivalent total-body absorbed dose (r ؍ 0.7, P ؍ 0.007). Further, at 19-75 months of follow-up time, seven patients showed higher MN yields than their respective levels before radiotherapy, indicating the persistence of radiation-induced residual cytogenetic damage. Our findings suggest that the MN yield in human PBLs offers a reliable acute and perhaps chronic biodosimeter for in vivo radiation dose estimation. After the completion of radiotherapy, the persistence of elevated MN yield in PBLs is a reflection of the surviving population of radiation-induced genetically aberrant cells.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2001
The frequency of micronucleated binucleate lymphocyte (MNBNC) was determined in the peripheral blood lymphocytes of patients suffering from various types of cancer before the onset of radiation treatment, middle (mid-) of the treatment and after completion of the treatment (post-treatment). The frequency of micronuclei increased significantly in the pretreatment sample of cancer patients when compared with the normal untreated healthy volunteers. During the middle of the radiotherapy an approximate two or >two-fold increase was observed in the micronuclei frequency in most of the patients when compared with the concurrent pretreatment samples. Immediately after the completion of treatment, the frequency of micronuclei further increased, and this increase was significantly higher than that of pretreatment and mid-treatment samples. Out of 27 patients analyzed, only nine patients did not have any history of smoking, tobacco chewing or alcohol consumption, while the remaining 18 patients had a history of either smoking, tobacco chewing or alcohol consumption or combination of two or all habits at the time of blood collection.
2021
Simple measurement of cytogenetic damage would be of great value for studying genetic risk factors, especially in radiotherapy for cancer patients. One cytogenetic technique that is easy and simple to quantify the damage caused by radiation exposure in cultured human lymphocytes is the micronucleus (MN). This research was conducted to study the induction of micronucleus (MN), Nucleoplasmic Bridge (NPB), and Nuclear Buds (NBUDs) in cancer patients after administration of fractionated radiation exposure total of 20 Gy. Peripheral blood lymphocyte samples obtained from eleven cancer patients as the study group and eleven from the healthy people as the control group were assessed. Both samples were then cultured and added cytochalasin-B to arrest cells during the cytokinesis stage. Its characteristics were observed in binucleated cells (BNC) with cytochalasin blocked micronuclei (CBMN) assay procedure. The number of MN, NPB, and NBUDs was evaluated per 1000 BNC for both the study group ...
Cytogenetic damage in peripheral blood lymphocytes of cancer patients prior to radiotherapy
Cancer Genetics and Cytogenetics, 1992
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Cytogenetic damage in peripheral blood lymphocytes of children exposed to pesticides in agricultural areas of the department of Cordoba, Colombia
Radiation Oncology Investigations, 1993
We obtained peripheral lymphocytes from both healthy donors (n = 7) and cancer patients (n = 14) for the cytokinesis-blocked micronucleus (MN) assay. Lymphocytes were irradiated with 13'Cs to 2 Gy. Cytochalasin B (6 &ml) was added to the incubation at 44 hr and the cells were harvested a t 72 hr. We found that compared to healthy donors, lymphocytes of cancer patients revealed no significant difference in the MN baseline level (P = 0.86). Apparently DNA damage manifested as MN in the lymphocytes of cancer patients is not more severe than that of healthy donors. In addition, 2 Gy in vitro irradiation of lymphocytes caused no difference in the MN formation between cancer patients and healthy donors (P = 0.9). Radiation induced cell cycle delay as evaluated by the number of mononucleate, binucleate, and cells with >2 nuclei and by the mitotic indices showed similar results in both populations. However, the difference for MN frequency in lymphocytes before and after 2 Gy in vitro irradiation was highly significant for both cancer patients and healthy donors (P = 0.0001). These studies in general indicate that the MN frequency in cytochalasin B-blocked human lymphocytes has the potential of serving as a quantitative biological dosimeter for the screening of radiation exposure to either healthy individuals or cancer patients.
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.
British Journal of Radiology, 2010
The purpose of this study was to evaluate the in vivo dose-response relation of chromosome aberration formation and distribution in a context of localised and fractionated radiotherapy. Cytogenetic analysis was applied to eight patients, all treated for the same tumour localisation; the same localisation was used to prevent the variability usually observed between patients treated with radiotherapy and to allow the corresponding roles of the size of irradiation field and of the dose rate to be studied. The yield of dicentrics, centric rings and fragments was measured in blood samples taken before treatment, during the course of radiotherapy and up to 6 months after. After the first fraction of radiotherapy, we observed that the whole-body dose estimated from the yield of dicentrics and rings was higher (0.35¡0.2 Gy) than the calculated equivalent whole-body dose (0.07¡0.04 Gy). By contrast, the partial-body dose derived from the Qdr (quotient of dicentrics and rings) model was estimated to be 2.2¡0.3 Gy, which agreed quite well with the dose delivered to the tumour (2.1¡0.1 Gy). We also found a correlation between the yield of induced chromosome aberrations and the target field size (p50.014). U-value analysis showed that the distribution of dicentrics and rings was overdispersed, despite the fractionation of the exposure, and a positive correlation between the U-value and the dose rate was observed (p50.017). Overall, these results suggest that the proportion of undamaged lymphocytes could increase with the dose rate.
Genetics and Molecular Biology, 2005
Scoring of unstable chromosome aberrations (dicentrics, rings and fragments) and micronuclei in circulating lymphocytes are the most extensively studied biological means for estimating individual exposure to ionizing radiation (IR), which can be used as complementary methods to physical dosimetry or when the latter cannot be performed. In this work, the quantification of the frequencies of chromosome aberrations and micronuclei were carried out based on cytogenetic analyses of peripheral blood samples from 5 patients with cervical uterine cancer following radiotherapy in order to evaluate the absorbed dose as a result of partial-body exposure to 60 Co source. Blood samples were collected from each patient in three phases of the treatment: before irradiation, 24 h after receiving 0.08 Gy and 1.8 Gy, respectively. The results presented in this report emphasize biological dosimetry, employing the quantification of chromosome aberrations and micronuclei in lymphocytes from peripheral blood, as an important methodology of dose assessment for either whole or partial-body exposure to IR.