PURPOSE: 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. MATERIALS AND 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.
PURPOSE: 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. MATERIALS AND 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.
Authors: Ryan T Kendall; Ludivine Renaud; John E Baatz; Maya Malaab; Xinh-Xinh Nguyen; Carol A Feghali-Bostwick Journal: J Proteomics Date: 2021-04-27 Impact factor: 3.855