The aim of this study was to investigate the relationship of chromosomal radiosensitivity and acute clinical side effects in 47 breast cancer patients who underwent radiotherapy for tumour treatment. The extent of clinical side effects has been used as an indicator for the individual radiosensitivity of each patient. Such established relationships would be of clinical relevance because they could represent a predictive factor that is required for an individualisation of radiotherapy .
Greve at al.  reasoned that neither measurement of radiation-induced apoptotic and necrotic cell death is detectable in immortalised lymphoblastoid derivatives nor cell death in blood lymphocytes is suitable to unequivocally predict the individual clinical radiosensitivity of cancer patients.
Premature chromosome condensation (G2 test) reveals practically indistinguishable levels of chromosomal breaks in AT and normal lymphoblastoid cells or lymphocytes, though lymphocytes of AT patients reveal an increased radiosensitivity measured by PCC(premature chromosome condensation) chromosome breaks .
Based on the micronucleus assay in cytokinesis-blocked lymphocytes, Mozdarani et al.  found significant differences between a control group and groups of breast cancer or oesophageal cancer patients, respectively, after in vitro irradiation with 3 Gy; nevertheless, radiosensitive individuals could not be identified in this study.
Interindividual radiosensitivity in blood lymphocytes of 14 healthy donors could not be detected with the micronucleus assay, nor with the G2 assay. It could not be decided whether the detected variation of both cytogenetic effects was due to interindividual variation of radiosensitivity, or to intraindividual variation . Hence it is promising to study chromosomal damage as a marker for cellular radiosensitivity because it is well established as a quantitative indicator for preceding radiation exposure [28–33]. We therefore have quantified chromosomal aberrations in blood samples from 47 tumour patients which have been irradiated with 3 Gy X-rays in vitro. The measured aberration frequencies showed for some patients significant deviations from the mean value for each aberration category (Figures 1 and 2). The presented approach is novel because in this study the use of an automated scoring system allowed an evaluation of 6829 metaphases which would facilitate to use this approach routinely in clinical testing. The validity of these scoring results is indicated by the highly significant correlations between each aberration categories.
The statistical analyses further revealed that four out of 47 patients exhibited a significantly elevated aberration frequency at least for one aberration category indicating an increased radiation response at the DNA repair level (Table 1). Interestingly, the dicentric frequencies were not significantly elevated in each of the four patients, but translocations showed a significant increase. Such discrepancies between translocation and dicentric yields after radiation exposure have already been described in several studies quantifying radiation-induced chromosome aberrations [32, 34]. In view of the correlation, it means that translocations show a more extensive response to radiation compared to dicentrics.
So far, Keller et al.  reported that among other cytogenetic parameters, the parameter "percentage of dicentric chromosomes" could neither serve as meaningful nor as significant criteria, since it showed a strong interindividual variability, whereas translocations were suitable indicators for detecting differences in blood lymphocytes from patients and controls irradiated in vitro with two different doses.
On the other hand there was found an indication for a reduced radiation response since significantly reduced aberration frequencies at least for one aberration category have been detected in four patients (Table 1). Thus based on cytogenetic results one would expect four patients with an enhanced and four patients with a reduced radiosensitivity in our study. In order to validate this assumption, clinical phenotypes were also considered. The comparison with acute clinical side effects (mainly skin reactions) demonstrated that none of the patients exhibiting significantly reduced aberration yields suffered from abnormal tissue reactions during or after radiotherapy reflecting the initial finding of a reduced radiosensitivity. However, among the four patients with elevated aberration frequencies three patients showed either a more severe side reaction of radiotherapy (patient 1) or a premature side reaction already after 10 Gy of irradiation (patients 7 and 17). Although such a co-incidence could not be found for patient 3, these results let assume that a relationship between cellular radiosensitivity measured as chromosome aberration yield in peripheral lymphocytes and acute clinical side reactions exists. Anyway, it could be demonstrated with statistical significance that a chromosome aberration test investigating translocations by FISH is suitable to identify individuals with shortened response time of radiation-induced skin reactions.
So far, only few studies exist reporting on similar relationships between acute clinical reactions and metaphase chromosome radiosensitivity. Dunst et al.  demonstrated that nine out of 26 radiotherapy patients showing elevated chromosome break frequencies suffered from an increased acute skin damage. Compared to our patient cohort they investigated more different tumour types leading to higher heterogeneity after in vitro exposure with 0.7 and 2.0 Gy in the study group . Similar results were reported by Popanda et al.  who detected 6 out of 113 radiotherapy patients with excessive acute skin reactions also showing significantly increased radiation-induced genomic changes detected by the COMET assay. However, a statistical correlation between genome alterations and acute side effects could not be demonstrated. Further studies reported an increased cellular radiosensitivity in radiotherapy patients using G0 and G2 assays [27, 35]. However, these did not register clinical side effects which limits the impact of their results. On the other hand in a recent study, Slonina et al.  could not find elevated acute or late side effects in cervix carcinoma patients whose cultured keratinocytes and fibroblasts exhibited increased micronucleus frequencies. Moreover, it has been demonstrated in several in vitro studies that the G0 micronucleus assay in blood lymphocytes using 3 Gy in vitro exposure , using 3.5 Gy in vitro exposure , and blood lymphocyte G2 assay using 0.4 Gy in vitro exposure , have limited reproducibility due to extended intraindividual variability. Limitations of the G2 assay, e.g. from interindividual variation, were also reported in a compilation from data of different studies .
In conclusion, a comparison of our findings with several published data suggests that measuring chromosomal radiosensitivity on translocation level in blood lymphocytes can be proposed to be used as a predictive assay for detection of radiosensitive individuals which should be developed further. Data from larger cohorts are needed to assess whether a particular aberration type is most sensitive to detect increased radiosensitivity. It would be also of interest to monitor chromosome aberrations in blood lymphocytes ex vivo at different times during radiotherapy to evaluate whether the occurrence of acute clinical side effects is related to increased aberration frequencies in a timely manner in order to detect a potential timely correlation, which would correspond to our findings from lymphocytes exposed in vitro.