Análise cromossômica dos linfócitos do sangue periférico e dos polimorfismos do gene de reparo do DNA XRCC1 em indivíduos com anemia falciforme.

Abstract

Sickle cell disease is an inherited disorder caused by a single nucleotide substitution in the β-globin gene. The clinical heterogeneity observed in sickle cell disease patients has been attributed to environmental and genetic factors. Patients with sickle cell disease are subjected to increased oxidative stress, particularly during vaso-occlusive crises and acute chest pain. Another possible cause of the oxidative stress in sickle cell diseases is the high concentrations 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 chromosomal aberrations in cultured lymphocytes from sickle cell disease 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 sickle cell disease, we investigated the frequency of chromosome damage in patients and the distribution of the DNA repair gene XRCC1 and its influence on chromosomal damage in sickle cells patients and healthy volunteers. Human blood samples were obtained from 15 patients and 15 healthy volunteers. The results show that patients presented a marked decrease in the mitotic index values compared with healthy volunteers and an increased percentage of aberrant metaphases. In the cytogenetic challenge assays, cisplatin-induced chromosomal damage in lymphocytes from patients was significantly higher than the frequency measured in healthy volunteers. The allele frequencies for 194Trp or 399Gln were not statistically different from patients and volunteers. There was no evidence that any of the alleles studied influenced the response to chromosomal aberrations or increased DNA sensitivity, except for an increased tendency in Arg/Gln individuals.