Impact of various parameters in detecting chromosomal aberrations by FISH to describe radiosensitivity.
OBJECTIVE
Analysis of radiation-induced chromosomal aberrations is regarded as the "gold standard" for classifying individual radiosensitivity. A variety of different parameters can be used. The crucial question, however, is to explore which parameter is suited best to describe the differences between patients with increased radiosensitivity and healthy individuals.


METHODS
In this study, five patients with severe radiation-induced late effects of at least grade 3, classified according to the Radiation Therapy Oncology Group (RTOG), and eleven healthy individuals were examined retrospectively. Peripheral blood lymphocytes were irradiated in vitro with 0.7 Gy and 2.0 Gy prior to cultivation and stained by means of three-color fluorescence in situ hybridization (FISH). The detailed analysis was focused on the number of breaks per metaphase, on breaks from complex chromosomal rearrangements per metaphase, as well as on the percentage of translocations, dicentric chromosomes, breaks, and excess acentric fragments-each in comparison with the total number of mitoses analyzed.


RESULTS
Using the number of breaks from complex chromosomal rearrangements after 2.0 Gy, radiosensitive patients as endpoint were clearly to be distinguished (p = 0.001) from healthy individuals. Translocations (p = 0.001) as well as breaks per metaphase (p = 0.002) were also suitable indicators for detecting differences between patients and healthy individuals. The parameters "percentage of dicentric chromosomes", "breaks", and "excess acentric fragments" in comparison to the total number of mitoses analyzed could neither serve as meaningful nor as significant criteria, since they showed a strong interindividual variability.


CONCLUSIONS
To detect a difference in chromosomal aberrations between healthy and radiosensitive individuals, the parameters "frequency of breaks per metaphase", "complex chromosomal rearrangements", and "translocations" are most suitable.
Keller
Ulrike
U
Division of Radiobiology, Department of Radiotherapy, Erlangen, Germany.
Kuechler
Alma
A
Liehr
Thomas
T
Müller
Elisabeth
E
Grabenbauer
Gerhard
G
Sauer
Rolf
R
Distel
Luitpold
L
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000097:blood* / Q000145:classification / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics* / Q000528:radiation effects; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity