Clinical, Molecular- and Cytogenetic Analysis of a Case of Severe Radio- Sensitivity

K.M.      Greulich-Bode; F.      Zimmermann; W.-U.      Muller; B.      Pakisch; M.      Molls; F.      Wurschmidt

doi:10.2174/138920212802510475

Abstract

In radiotherapy the normal tissue reaction is often a limiting factor for radiation treatment. Still there is no screening method, which predicts normal tissue reaction on radiotherapy, especially in comparison to tumor tissue, and therefore allows tailoring of the radiation dose to each patient. Here, we present a case of severe radiation-related side effects. We applied classical cytogenetic techniques (Giemsa-banding and staining of centromeric regions), the comet assay as well as multicolor fluorescence in situ hybridization on peripheral blood lymphocytes of this patient in order to determine the radio-sensitivity on the DNA level and to correlate these findings with the clinical outcome. Our investigations revealed abnormalities on chromosome 9, deficiencies in the DNA-repair capacity after radiation exposure and a high number of radiation induced chromosomal aberrations. A detected high amount of residual damage two or three hours after radiation exposure and repair as well as the high number of chromosomal aberrations (ChAs) suggests a correlation between repair capacity and radiation induced ChAs. We concluded that the detected abnormalities might serve as a genetic basis for the radio-sensitive phenotype of this patient. Taken together this report strengthens the idea that intensive DNA genomic analysis of individual patients can serve as the basis for more favourable treatment of cancer patients.

Keywords: Radiation therapy, DNA damage and repair, Double strand breaks, Comet assay, Radiation induced chromosomal aberrations, M-FISH, radio-sensitivity, situ hybridization, Giemsa-Trypsin-Giemsa, centromere