ABSTRACT
BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate genotoxicity and mutagenicity in peripheral blood and buccal mucosal cells in mucopolysaccharidosis (MPS) I, II or VI patients. METHODS: A total of 12 patients with MPS type I, II and VI attended at the Institute of Genetics and Inborn Errors of Metabolism treated with enzyme replacement therapy (ERT) and 10 healthy control volunteers were included in this study. Mechanically exfoliated cells from cheek mucosa (left and right side) were used to micronucleus test and single cell gel (comet) assay in peripheral blood cells. RESULTS: The results of this study detected the presence of genetic damage in peripheral blood for all individuals with MPS treated with ERT, regardless of type of MPS as depicted by tail moment results. In addition, an increased number of micronucleated cells were found in buccal cells of MPS type II patients. It was also observed an increase of other nuclear alterations closely related to cytotoxicity as depicted by the frequency of pyknosis, karyolysis and karyorrhexis in buccal mucosa cells of MPS VI patients (p < 0.05). CONCLUSION: Taken together, such results demonstrate that metabolic alterations induced by the enzymatic deficiency characteristic of MPS associated with ERT therapy can induce genotoxicity and mutagenicity in peripheral blood and buccal mucosa cells, respectively. This effect appears to be more pronounced to MPS II.
Subject(s)
Cell Nucleus/pathology , Chromatin/pathology , DNA Damage , DNA Fragmentation , Mucopolysaccharidosis II/pathology , Mucopolysaccharidosis IV/pathology , Mucopolysaccharidosis I/pathology , Adolescent , Adult , Blood Cells/pathology , Brazil , Cell Nucleus Shape , Child , Child, Preschool , Cytogenetic Analysis , Enzyme Replacement Therapy , Female , Humans , Male , Mouth Mucosa/pathology , Mucopolysaccharidosis I/blood , Mucopolysaccharidosis I/genetics , Mucopolysaccharidosis I/therapy , Mucopolysaccharidosis II/blood , Mucopolysaccharidosis II/genetics , Mucopolysaccharidosis II/therapy , Mucopolysaccharidosis IV/blood , Mucopolysaccharidosis IV/genetics , Mucopolysaccharidosis IV/therapy , Young AdultABSTRACT
BACKGROUND: Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of alfa-iduronidase (IDUA), which leads to intralysosomal accumulation of glysosaminoglycans. Evidences point secondary events like oxidative stress on lysosomal storage diseases including MPS I. Patients with MPS I present a wide range of oral clinical manifestations, including tongue hypertrophy, hypertrophyc alveolar process, and carious teeth. However, the mechanisms by which these alterations occur are still not fully understood. The aim of this study was to analyze the proliferative activity as well as apoptosis in tongue mucosa cells from murine model of MPS I. MATERIALS AND METHODS: Protein expression of apoptotic markers such as p53, bcl-2 and bax were evaluated in this setting. Ki-67 was used as a proliferative marker. All analyses were made by immunohistochemistry in tongue cells. Statistical analysis was perfomed by Kruskal-Wallis non-parametric test followed by the Dunn's test. P < 0.05 was considered for statistic significance. RESULTS: Histopathological analysis revealed no remarkable differences in tongue mucosa on MPS I mice when compared to control. By contrast, our results demonstrated that bcl-2 immunoexpression was decreased in mice tongue mucosa cells of MPS I mice. p53, bax and ki-67 immunoexpresssion did not show significant differences among controls and MPS I mice. CONCLUSION: Taken together, our results suggest that IDUA deficiency, which characterizes MPS I, may induce apoptosis in mice tongue cells as a result of bcl-2 down regulation.
