Introduction:Hodgkin's lymphoma (HL) is a lymphoid malignancy with a worldwide incidence is 2-4/100,000 individuals/year. HL represents 5% of all childhood cancers and is 30-40% of all malignant lymphomas. Treatment for HL involves a combination of radiation and chemotherapy. One of the most common treatment schemes uses ABVD (adriamycin, bleomycin, vinblastine, dacarbazine), a cocktail of genotoxic agents. Although survival rate for HL is up to 95%, cancer therapy could produce persistent genetic damage in the survivors.Objective: The goal of this study is to determine the time course of chromosomal damage in lymphocytes of patients with HL before, during and after ABVD/radiotherapy. Material and methods: Five patients diagnosed with HL provided peripheral blood samples before, during and one year after ABVD chemotherapy. In addition, 5 healthy individuals provided a single blood sample. All participants in the study signed informed consent. Chromosomal aberrations were evaluated by M-FISH (SpectraVysion) in 50-100 karyotypes per sample. Spectral karyotyping for each cell was analysed with Isis software. Statistical comparisons were done with the Kruskal-Wallis and Mann-Whitney U tests and a p < 0.05 was considered significant.Results: Average frequencies of structural chromosomal aberrations (CA) in samples from patients with HL were 6.3, 7.1 and 23.0% before treatment, during, and one year after treatment, respectively. CA frequency in healthy individuals was 2.4%. A significant difference (p < 0.002) was observed when comparing groups. Chromosomal damage was observed in all samples, and rejoined structural chromosomal aberrations (RCA), such as translocations and dicentrics, were the most common type. No clonal aberrations were observed.Conclusions: Our study showed that ABVD cause genotoxic damage in peripheral blood lymphocytes of HL patients. Interestingly, the highest frequency of RCA/cell was observed in samples analyzed one year after treatment and this was significantly different from what was found before treatment (23% vs 6%). Both rejoined and non-rejoined aberrations are observed one year after treatment indicating that new aberrations are continuously produced and that there may be alterations affecting genes involved in DNA repair. These results suggest that ABVD/radiotherapy causes sublethal damage in hematopoietic stem cells and can lead to persistent genomic instability.Financial support: 099-CONACYT-Salud.http://dx.
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