Chromosomal Radiosensitivity Analyzed by FISH in Lymphocytes of Prostate Cancer Patients and Healthy Donors

Abstract

It is known that about 5-10% of cancer patients show severe clinical side effects during and after radiotherapy due to enhanced sensitivity to ionizing radiation. Identification of those radiosensitive individuals by a reliable in vitro assay before onset of treatment would have a great impact on successful radiotherapy. We compared the radiosensitivity of the chromosomes 2, 11 and 17 in prostate cancer patients with and without severe side effects after radiotherapy and in age-matched healthy donors. Each cohort consisted of at least 10 donors. Peripheral blood lymphocytes were irradiated ex vivo with 0.5, 1 und 2 Gy ((137)Cs γ rays). We investigated the radiosensitivity of the chromosomes 2, 11 and 17 by scoring of 100 FISH painted metaphases for each dose point and donor group. Statistical analyses were performed by nonparametric tests as Mann-Whitney test and Kruskal-Wallis ANOVA, paired Wilcoxon rank test, χ(2) goodness-of-fit test and Spearman rank-order correlation at a significance level of P < 0.05. Analysis of the overall aberration yield revealed no significant differences between any donor groups. The translocation frequencies of the chromosomes 2, 11 and 17 coincided with their relative size. Thus, none of the chromosomes analyzed were more or less radiosensitive with respect to the genomic translocation frequency. Additionally, neither of the chromosomes showed enhanced or diminished radiosensitivity in one of the donor groups. Furthermore, variance analyses revealed that the distribution pattern of the aberrations per donor did not differ in each donor group even after exposure to 2 Gy. Prostate cancer patients with and without side effects cannot be distinguished from healthy donors based on aberration yield after irradiation with γ rays.

Differences in Cytogenetic Sensitivity to Ionizing Radiation in Newborns and Adults

“…Even though an age effect was not evident among adults, interindividual variation due to intrinsic genetic factors may still influence radiation responses (18). A recent report by Schmitz et al (19) indicates that patients with and without radiotherapy-induced side effects cannot be distinguished from healthy subjects, these results argue against the existence of substantial inter-individual sensitivity of adults to ionizing radiation. Of further interest is the observation by Ohtaki et al (20) that human fetuses exposed to ionizing radiation from the atomic bombs do not have elevated frequencies of translocations in their peripheral blood lymphocytes, except for a small increase at doses below 0.1 Sv.…”

Prediction of the Acute or Late Radiation Toxicity Effects in Radiotherapy Patients Using Ex Vivo Induced Biodosimetric Markers: A Review

“…It should be noted, that in two studies using the MN test [77,87] and in one using the ChA test [75], which did not detect a predictive value of cytogenetics, the irradiated lymphocytes were cultured longer than is normally done according to biodosimetry standards [39] and without an indicator for cell cycle (such as BrdU for ChAs), even though the doses used for ex vivo irradiation (2-3.5 Gy) were not high enough to cause a significant mitotic delay. The absence of correlation between cytogenetic and clinical radiosensitivity in these reports can, therefore, be partially attributed to aberration-free cells surviving into 2nd divisions while damaged cells would more likely be eliminated in the 1st division.…”

Assessment of Individual Radiosensitivity in Inhabitants of Takandeang Village － A High Background Radiation Area in Indonesia

“…Until now, there have not been many studies on the correlation between Arg72Pro and radiosensitivity. Comprehensive studies about the association between TP53 Arg72Pro polymorphism and radiosensitivity were already performed by Alsbeih et al [8,28]. In 2007 Alsbeih et al observed an increase of survival in fibroblast cells using clonogenic assay after exposed to single radiation dose ranging from 0 to 4 Gy in cells containing Proline coding allele in TP53 (Arg72Pro) gene.…”

“…Until now the chromosomal aberration assay is the most commonly used assay to predict individual radiosensitivity. In brief, lymphocytes are irradiated in vitro in the G 0 phase and then stimulated to proceed in the cell cycle [8]. Another technique also commonly used for the assessment of individual radiosensitivity is G 2 micronucleus (MN) assay.…”