Genotoxic effects of radiotherapy and chemotherapy on circulating lymphocytes in patients with Hodgkin's disease.
OBJECTIVE
The aim of this study was to find out the structural chromosomal changes in somatic cells after chemotherapy (CT) with or without radiotherapy (RT).


METHODS
This prospective study included 30 Hodgkin's disease (HD) patients. The patients of Group I(1) had only MOPP/ABV CT. The patients of Group II(2) also had irradiation. Group III(3) (control group) consisted of healthy subjects without any reported malignant disease. Mutagenetic testing was performed at the time of diagnosis and was repeated immediately after treatment and again 6 months later. The following tests were applied: structural 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 of 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 chromosome damage persisted even 6 months after combined RT and CT. The damage in the genome of individual cells was in some cases even greater than immediately after treatment. The possible risk of neoplastic transformation posed by these heavily damaged cells, if viable, due to the changes in the expression of oncogenes or tumour suppresser genes, is discussed.
Bilban-Jakopin
C
C
Department of Radiation Oncology, Institute of Oncology, SI-1000 Ljubljana, 2, Zaloska, Slovenia. cjakopin@onko-i.si
Bilban
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M
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D003131:Combined Modality Therapy; D004249:DNA Damage; D006689:Hodgkin Disease / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000528:radiation effects*; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000528:radiation effects; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000528:radiation effects
D000970:Antineoplastic Agents