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Spontaneous and radiation-induced chromosomal instability and persistence of chromosome aberrations after radiotherapy in lymphocytes from prostate cancer patients.

Hille A, Hofman-Hüther H, Kühnle E, Wilken B, Rave-Fränk M, Schmidberger H, Virsik P - Radiat Environ Biophys (2009)

Bottom Line: 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.This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks.

View Article: PubMed Central - PubMed

Affiliation: Abteilung für Strahlentherapie und Radioonkologie, Universitätsmedizin Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany.

ABSTRACT
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.

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Chromosome aberration yields per cell (peripheral lymphocytes) in prostate cancer patients compared to healthy donors after ex vivo irradiation with D = 3 Gy. Blood samples of cancer patients were taken before radiotherapy. Yields of dicentric chromosomes (ydic) and excess acentric fragments (yac (ex)) were determined in Giemsa-stained metaphases. Yields of simple exchanges (ySE), representing sums of dicentric chromosomes and reciprocal translocations were evaluated in metaphases with painted chromosomes 2 and 4. Data are presented as box plots with each box enclosing 50% of the overall data. Median value of the variable is displayed as a horizontal line. The top and the bottom of the box mark the limits of ±25% of the variable population. The lines extending from the top and bottom of each box denote the minimum and maximum values within the data set that are located within an acceptable range (points with values either greater than the upper quartile +1.5x interquartile distance or less than lower quartile −1.5x interquartile distance); outliers that are not included are represented by circles
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Fig2: Chromosome aberration yields per cell (peripheral lymphocytes) in prostate cancer patients compared to healthy donors after ex vivo irradiation with D = 3 Gy. Blood samples of cancer patients were taken before radiotherapy. Yields of dicentric chromosomes (ydic) and excess acentric fragments (yac (ex)) were determined in Giemsa-stained metaphases. Yields of simple exchanges (ySE), representing sums of dicentric chromosomes and reciprocal translocations were evaluated in metaphases with painted chromosomes 2 and 4. Data are presented as box plots with each box enclosing 50% of the overall data. Median value of the variable is displayed as a horizontal line. The top and the bottom of the box mark the limits of ±25% of the variable population. The lines extending from the top and bottom of each box denote the minimum and maximum values within the data set that are located within an acceptable range (points with values either greater than the upper quartile +1.5x interquartile distance or less than lower quartile −1.5x interquartile distance); outliers that are not included are represented by circles

Mentions: Next, we analysed aberration yields in Giemsa-stained lymphocytes from the same 102 untreated patients and healthy donors irradiated ex vivo with 200 kV X-rays and a dose D = 3 Gy. In the patient and control groups, 16,000 and 2,600 cells, respectively, were scored in Giemsa-stained metaphases. These data are presented in Fig. 2 as box plots, each box enclosing 50% of all collected data. The median values are displayed as horizontal lines within the corresponding boxes. Using Student’s t test for comparison of two means of Poisson distributions, we found that the yields of dicentric chromosomes per cell and those of excess acentric fragments per cell, as compared in patients and healthy donors, were not significantly different. Thus, in the studied prostate cancer patients, only spontaneous chromosomal instability could be revealed. Radiation-induced chromosomal instability, which would indicate an impaired repair of DNA double-strand breaks, was not observed.Fig. 2


Spontaneous and radiation-induced chromosomal instability and persistence of chromosome aberrations after radiotherapy in lymphocytes from prostate cancer patients.

Hille A, Hofman-Hüther H, Kühnle E, Wilken B, Rave-Fränk M, Schmidberger H, Virsik P - Radiat Environ Biophys (2009)

Chromosome aberration yields per cell (peripheral lymphocytes) in prostate cancer patients compared to healthy donors after ex vivo irradiation with D = 3 Gy. Blood samples of cancer patients were taken before radiotherapy. Yields of dicentric chromosomes (ydic) and excess acentric fragments (yac (ex)) were determined in Giemsa-stained metaphases. Yields of simple exchanges (ySE), representing sums of dicentric chromosomes and reciprocal translocations were evaluated in metaphases with painted chromosomes 2 and 4. Data are presented as box plots with each box enclosing 50% of the overall data. Median value of the variable is displayed as a horizontal line. The top and the bottom of the box mark the limits of ±25% of the variable population. The lines extending from the top and bottom of each box denote the minimum and maximum values within the data set that are located within an acceptable range (points with values either greater than the upper quartile +1.5x interquartile distance or less than lower quartile −1.5x interquartile distance); outliers that are not included are represented by circles
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2822223&req=5

Fig2: Chromosome aberration yields per cell (peripheral lymphocytes) in prostate cancer patients compared to healthy donors after ex vivo irradiation with D = 3 Gy. Blood samples of cancer patients were taken before radiotherapy. Yields of dicentric chromosomes (ydic) and excess acentric fragments (yac (ex)) were determined in Giemsa-stained metaphases. Yields of simple exchanges (ySE), representing sums of dicentric chromosomes and reciprocal translocations were evaluated in metaphases with painted chromosomes 2 and 4. Data are presented as box plots with each box enclosing 50% of the overall data. Median value of the variable is displayed as a horizontal line. The top and the bottom of the box mark the limits of ±25% of the variable population. The lines extending from the top and bottom of each box denote the minimum and maximum values within the data set that are located within an acceptable range (points with values either greater than the upper quartile +1.5x interquartile distance or less than lower quartile −1.5x interquartile distance); outliers that are not included are represented by circles
Mentions: Next, we analysed aberration yields in Giemsa-stained lymphocytes from the same 102 untreated patients and healthy donors irradiated ex vivo with 200 kV X-rays and a dose D = 3 Gy. In the patient and control groups, 16,000 and 2,600 cells, respectively, were scored in Giemsa-stained metaphases. These data are presented in Fig. 2 as box plots, each box enclosing 50% of all collected data. The median values are displayed as horizontal lines within the corresponding boxes. Using Student’s t test for comparison of two means of Poisson distributions, we found that the yields of dicentric chromosomes per cell and those of excess acentric fragments per cell, as compared in patients and healthy donors, were not significantly different. Thus, in the studied prostate cancer patients, only spontaneous chromosomal instability could be revealed. Radiation-induced chromosomal instability, which would indicate an impaired repair of DNA double-strand breaks, was not observed.Fig. 2

Bottom Line: 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.This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks.

View Article: PubMed Central - PubMed

Affiliation: Abteilung für Strahlentherapie und Radioonkologie, Universitätsmedizin Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus