Radiation-induced micronucleus formation in human skin fibroblasts of patients showing severe and normal tissue damage after radiotherapy.
OBJECTIVE
Treatment schedule and total dosage in radiation therapy is based on the tumoricidal doses and the tolerance dose of the perifocal normal tissue. Since large-scale variations occur between the patients concerning the side effects, one of the major goals of radiation research recently has been the development of a predictive in vitro assay. This paper is a contribution to that effort.


METHODS
Skin fibroblasts of patients with normal-tissue reactions or acute and/or late increased side effects and cell lines of four individuals carrying the heritable disease ataxia telangiectasia were irradiated in vitro. The formation of micronuclei was chosen as biological endpoint and the results were compared with the clinically observed side effects.


RESULTS
In general, a radiation dose-dependent increase in micronucleus frequency was found. The cells of the majority of the sensitive patients, as well as those of homozygous and heterozygous ataxia telangiectasia individuals, showed a higher micronucleus induction than the average of the donors with normal sensitivity.


CONCLUSIONS
The micronucleus test seems to be a very promising tool in the evaluation of radiation sensitivity prior to therapy. However, larger studies are needed to confirm these findings and to optimize the methodology, and it is presumed that a final predictive assay will consist of a combination with other test systems.
Nachtrab
U
U
Department of Toxicology, University of Würzburg, Germany.
Oppitz
U
U
Flentje
M
M
Stopper
H
H
D000328:Adult; D000368:Aged; D001260:Ataxia Telangiectasia / Q000235:genetics; D006801:Humans; D015162:Micronucleus Tests; D008875:Middle Aged; D011832:Radiation Injuries / Q000473:pathology*; D011878:Radiotherapy / Q000009:adverse effects*; D012867:Skin / Q000528:radiation effects*