Genotoxic effects of radiotherapy and chemotherapy on circulating lymphocytes in patients with Hodgkin's disease

Purpose: The aim of this study was to find out the structural chromosomal c hanges in somatic cells after chemotherapy (CT) with or without radiotherap y (RT). Methods and Materials: This prospective study included 30 Hodgkin's disease (HD) patients. The patients of Group I-1 had only MOPP/ABV CT. The patient s of Group II2 also had irradiation. Group III3 (control group) consisted o f healthy subjects without any reported malignant disease. Mutagenetic test ing was performed at the time of diagnosis and was repeated immediately aft er treatment and again 6 months later. The following tests were applied: st ructural chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronucleus (MN) tests. Results: Prior to treatment, the chromosome damage in our patients was not higher than that in the control group. Immediately after the complete treatment, we observed a strong inhibition o f the mitotic activity of lymphocytes as well as a significant increase in the frequency of CA, MN and SCE in the Groups I and II. In patients treated by RT, we found statistically significant differences between the Groups I and II in MN (P < 0.005) and CA frequencies (P < 0.005), and an increased number of dicentrics (P = 0.021). Six months after the complete treatment, the mitotic activity was found to be nearly normal, but chromosome damage occurred. CA and SCE values did not differ much from the values measured immediately after treatment, whereas MN values decreased without returning to the baseline levels. The chromosom e damage persisted even 6 months after combined RT and CT. The damage in th e genome of individual cells was in some cases even greater than immediatel y after treatment. The possible risk of neoplastic transformation posed by these heavily damaged cells, if viable, due to the changes in the expressio n of oncogenes or tumour suppresser genes, is discussed. (C) 2001 Elsevier Science B.V. All rights reserved.