RESUMO
Recent studies have suggested that chemokines contribute to the initiation and development of acute pancreatitis. We evaluated the relationship between IL-10 gene polymorphisms (-1082A/G and -819T/C) and development of acute pancreatitis in the Chinese population, in order to provide data for screening high-risk Chinese individuals. In total, 182 patients with confirmed cases of acute pancreatitis and 262 control subjects were recruited from the Shaanxi Provincial People's Hospital between April 2012 and December 2014. IL-10 gene polymorphisms at positions -1082A/G and -819T/C were examined using the polymerase chain reaction-restriction fragment length polymorphism method. Through multiple-logistic regression analysis, the GG genotype in IL-10 -1082A/G could influence the susceptibility to acute pancreatitis compared to the AA genotype, and the adjusted OR (95%CI) was 2.68 (1.34-5.39) (P = 0.002). Individuals who carried the AG+GG genotype of IL-10 -1082A/G were associated with greater risk for acute pancreatitis compared to the wide-type genotype, and the adjusted OR (95%CI) was 1.64 (1.09-2.46). However, no significant difference in susceptibility to acute pancreatitis was found between the IL-10 gene polymorphism at -819T/C. In conclusion, this study demonstrates that the IL-10 -1082A/G gene polymorphism contributes to the development of acute pancreatitis.
Assuntos
Interleucina-10/genética , Pancreatite/genética , Idoso , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Chlorambucil (CLB) is an alkylating agent commonly used in the treatment of several neoplastic disorders. The mechanisms underlying resistance to this drug are not fully defined. We used the DNA alkaline elution technique to study cross-link formation in the wild type (K1) and a CLB-resistant (ChlR) Chinese hamster ovary cell line. [14C]CLB was used to measure drug uptake. The CLB-resistant cells were found to have negligible DNA cross-link formation compared to K1 cells at all time points tested. There was a correlation between the resistance to CLB and the decreased ability of resistant cells to form DNA cross-links. Results of drug uptake experiments excluded altered CLB accumulation as the basis for these findings. Assays of O6-alkylguanine transferase and topoisomerase. II provide evidence against a role of these enzymes in CLB resistance. These studies suggest that the mechanism of CLB cytotoxicity involves the formation of DNA cross-links. Reduced cross-link formation may confer resistance to CLB.
