Limits...
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.

Show MeSH

Related in: MedlinePlus

a Spontaneous yields of excess acentric fragments per 100 cells (peripheral lymphocytes) in prostate cancer patients compared to healthy donors. Prostate cancers patients are divided into patients with prostate only (open circles) and patients with prostate and nodal disease (open triangles). Yields of excess acentric fragments (yac (ex)) were determined in Giemsa-stained metaphases. Data are presented as individual data points plotted depending on age (open symbols = patients; closed diamonds = healthy donors). b Spontaneous yields of chromosome aberrations per cell (peripheral lymphocytes) in prostate cancer patients compared to healthy donors. 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. The corresponding 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 vertical 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


getmorefigures.php?uid=PMC2822223&req=5

Fig1: a Spontaneous yields of excess acentric fragments per 100 cells (peripheral lymphocytes) in prostate cancer patients compared to healthy donors. Prostate cancers patients are divided into patients with prostate only (open circles) and patients with prostate and nodal disease (open triangles). Yields of excess acentric fragments (yac (ex)) were determined in Giemsa-stained metaphases. Data are presented as individual data points plotted depending on age (open symbols = patients; closed diamonds = healthy donors). b Spontaneous yields of chromosome aberrations per cell (peripheral lymphocytes) in prostate cancer patients compared to healthy donors. 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. The corresponding 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 vertical 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: The aberration yields in lymphocytes of 102 untreated prostate cancer patients were analysed in Giemsa-stained metaphase cells. For comparison, aberration yields of ten age-matched healthy donors were analysed, as well. In the patient and control groups, 12,120 and 2,200 cells were scored, respectively. Aberration yields per cell were calculated for dicentric chromosomes (ydic) and for excess acentric fragments (yac (ex)). Data are presented in Fig. 1a, b as individual values, depending on age, and as box plots, with 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 in patients and healthy donors were not significantly different (P = 0.4). The yields of excess acentric fragments were significantly different in these two groups (P = 0.05), with increased rates in the patient group. To determine whether aberration yields were affected by extension of the disease, we also compared patients with prostate only or with prostate and nodal disease. Using Student’s t test as described above, we found no significant differences (P = 0.4) between patients with prostate only or with prostate and nodal disease. Individual data are shown in Fig. 1a.Fig. 1


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)

a Spontaneous yields of excess acentric fragments per 100 cells (peripheral lymphocytes) in prostate cancer patients compared to healthy donors. Prostate cancers patients are divided into patients with prostate only (open circles) and patients with prostate and nodal disease (open triangles). Yields of excess acentric fragments (yac (ex)) were determined in Giemsa-stained metaphases. Data are presented as individual data points plotted depending on age (open symbols = patients; closed diamonds = healthy donors). b Spontaneous yields of chromosome aberrations per cell (peripheral lymphocytes) in prostate cancer patients compared to healthy donors. 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. The corresponding 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 vertical 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

Show All Figures
getmorefigures.php?uid=PMC2822223&req=5

Fig1: a Spontaneous yields of excess acentric fragments per 100 cells (peripheral lymphocytes) in prostate cancer patients compared to healthy donors. Prostate cancers patients are divided into patients with prostate only (open circles) and patients with prostate and nodal disease (open triangles). Yields of excess acentric fragments (yac (ex)) were determined in Giemsa-stained metaphases. Data are presented as individual data points plotted depending on age (open symbols = patients; closed diamonds = healthy donors). b Spontaneous yields of chromosome aberrations per cell (peripheral lymphocytes) in prostate cancer patients compared to healthy donors. 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. The corresponding 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 vertical 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: The aberration yields in lymphocytes of 102 untreated prostate cancer patients were analysed in Giemsa-stained metaphase cells. For comparison, aberration yields of ten age-matched healthy donors were analysed, as well. In the patient and control groups, 12,120 and 2,200 cells were scored, respectively. Aberration yields per cell were calculated for dicentric chromosomes (ydic) and for excess acentric fragments (yac (ex)). Data are presented in Fig. 1a, b as individual values, depending on age, and as box plots, with 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 in patients and healthy donors were not significantly different (P = 0.4). The yields of excess acentric fragments were significantly different in these two groups (P = 0.05), with increased rates in the patient group. To determine whether aberration yields were affected by extension of the disease, we also compared patients with prostate only or with prostate and nodal disease. Using Student’s t test as described above, we found no significant differences (P = 0.4) between patients with prostate only or with prostate and nodal disease. Individual data are shown in Fig. 1a.Fig. 1

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