Reciprocal translocations in patients with testicular seminoma before and after radiotherapy

Abstract

Purpose: The evaluation of radiation-induced chromosomal translocations in peripheral lymphocytes using fluorescent in situ hybridization is a promising method for retrospective dosimetry after a radiation accident. We evaluated the genomic frequency of chromosomal translocations in patients with testicular seminoma who received adjuvant radiotherapy to the retroperitoneal lymph nodes, to evaluate the time–effect relationship of radiation-induced stable aberrations after partial body irradiation. Methods: In 13 patients, peripheral lymphocytes could be evaluated before radiotherapy and at several time points after radiotherapy. In 17 additional patients, lymphocyte samples were obtained after radiotherapy. Thirteen healthy men served as age-matched controls for the aberration frequency before radiotherapy. Fluorescent in situ hybridization was performed using whole chromosome probes against chromosomes No. 4, No. 6, and No. 7. Results: Nearly all patients displayed an increased spontaneous rate of genomic translocations ( F G ) before radiotherapy compared to age-matched, healthy men. The difference was significant in the paired ranks test ( p < 0.0001). After adjuvant radiotherapy, the F G increased 2- to 8-fold in individual patients. Within 20 months after radiotherapy, the F G returned to pretherapeutic levels. Conclusions: The frequency of genomic translocations after partial body irradiation is time dependent. A persistence of chromosomal aberrations, which is to be expected after total body irradiation, could not be observed. It is likely that the dose and the volume of the irradiated bone marrow are playing a role in the persistence of stable chromosomal aberrations. Patients with testicular seminoma displayed an increased frequency of spontaneous genomic translocations before the initiation of radiotherapy. This chromosomal instability might be related to the known increased rate of secondary cancers in this patient group.