Sensitivity to cisplatin-induced mutations and elevated chromosomal aberrations in lymphocytes from sickle cell disease patients |
| |
Authors: | Polyanna Miranda Alves Paulo Roberto Juliano Martins Francisca da Luz Dias Rommel Mario Rodríguez Burbano Maria de Lourdes Pires Bianchi Lusânia Maria Greggi Antunes |
| |
Institution: | Departamento de Ciências Biológicas, Universidade Federal do Triangulo Mineiro, Uberaba, MG, Brazil. |
| |
Abstract: | Sickle cell disease (SCD) is an inherited disorder caused by a single nucleotide substitution in the β-globin gene. The clinical
heterogeneity observed in SCD patients has been attributed to environmental and genetic factors. The patients are subjected
to increased oxidative stress, particularly during vaso-occlusive crises and acute chest pain. Another possible cause of oxidative
stress in SCD is the high concentration of iron in the patients’ plasma. The increase in oxidative stress could be a relevant
risk factor for mutagenesis and carcinogenesis. Studies on the frequency of basal chromosomal aberrations in cultured lymphocytes
from SCD patients have not been reported so far. In order to contribute to the understanding of the role of the different
biomarkers and their relationship with the extremely variable clinical manifestation of SCD, we investigated the frequency
of chromosome damage in peripheral lymphocytes from sickle cells patients and healthy controls. We found an increased frequency
of chromosome damage and percentage of aberrant metaphases in these patients when compared with control subjects, even at
basal values (p < 0.05). In the cytogenetic sensitivity assay, the results showed that these patients presented a marked decrease in the
mitotic index values compared with healthy controls. Cisplatin-induced chromosomal damage in lymphocytes from these patients
was significantly higher than the frequency measured in healthy controls. The results obtained in the present study showed
that more investigations are needed in order to elucidate the susceptibility to genomic instability of SCD patients. |
| |
Keywords: | Sickle cell Chromosome aberrations Cisplatin Genotoxicity Lymphocytes |
本文献已被 PubMed SpringerLink 等数据库收录! |