RESUMO
BACKGROUND: One of the principle symptoms of lead poisoning is the development of neurological disorders. Neuronal response is closely related to DNA methylation changes. Aim. In this study, we estimated p16 methylation in nine individuals exposed to lead using methylation-specific polymerase chain reaction followed by analysis of the methylated cytosine content of the product by thermal denaturation. RESULTS: We found that, based on lead blood concentration, lead-exposed individuals were divided into two groups. Among highly exposed individuals (blood Pb(2+) concentration = 51-100 microg/dL), we observed complete CpG methylation, whereas for low Pb(2+) concentrations (blood Pb(2+) concentration = 6-11 microg/dL), we observed partial methylation. CONCLUSION: Our results show that among lead-overexposed individuals, p16 methylation is frequent and extensive, and suggest that DNA methylation could be involved in the mechanism by which lead induces neurotoxicity.
Assuntos
Metilação de DNA/efeitos dos fármacos , Genes p16/efeitos dos fármacos , Intoxicação do Sistema Nervoso por Chumbo em Adultos/fisiopatologia , Exposição Ocupacional/efeitos adversos , Regiões Promotoras Genéticas , Adulto , Estudos de Casos e Controles , Ilhas de CpG/efeitos dos fármacos , Citosina/metabolismo , Humanos , Chumbo/sangue , Chumbo/toxicidade , Intoxicação do Sistema Nervoso por Chumbo em Adultos/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
Modern treatment protocols lead to complete remission in a high proportion of patients with childhood acute lymphoblastic leukemia (ALL). However, a large number of them show a relapse of the disease. Treatment failure in these patients is mainly attributable to de novo or acquired resistance to a wide variety of cytotoxic drugs, which is called multi drug resistance (MDR). Expression of multi drug resistance 1 gene (MDR1) is implicated in the drug-resistance mechanism. In order to contribute further information we present a rare case of a 15-month old girl with newly diagnosed CALLA positive pre-B acute lymphoblastic leukemia with favourable prognostic factors at diagnosis who experienced a relapse of the disease. Using reverse transcriptase polymerase chain reaction method, m-RNA expression of the MDR1 gene upon relapse, was five-fold compared with that at diagnosis. This is the first report on increased mRNA expression at relapse in a paired sample of a child with ALL in our region.
