Abstract:
Objective To explove the relationship of the promoter 5' CpG island methylation of mismatch repair gene hMLH1 and hMSH2 and the mutation of their exon12 with the effect of arsenism development cause by coal-burning, and also the process of canceration.
Methods A total of 110 cases of arsenism patients were selected as case group, classified as mild, moderate and severe subgroups according to their clinical diagnosis, and also divided into non-cancerous and carcinoma subgroups according to the pathology of their skin lesions. Methylation status of the hMLH1 and hMSH2 promoter region were assayed by methylation-specific polymerase chain reaction (MSP)in peripheral blood of 105 arsenism patients and 82 normal controls. The mutations of hMLH1 and hMSH2 exon12 were analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)in peripheral blood DNA of 110 arsenism patients and 110 normal controls.
Results ① The positive rates of hMSH2 methylation were 11.76%, 16.28% and 32.14% in mild, moderate and severe patients respectively, all significantly higher than those in controls, and the rate in severe patients were significantly higher than that in moderate. The positive rates of hMLH1 and hMSH2 were 11.11% and 27.78% in non-cancerous and carcinoma groups respectively, both significantly higher than that in controls. With the severity of clinical condition and skin lesions the positive rates of hMLH1 and hMSH2 methylation increased. ② There were no mutations of mismatch repair gene hMLH1and hMSH2 exon12 in patients and controls.
Conclusion The promoter hypermethylation of the mismatch repair gene hMLH1and hMSH2 is an early incident in the development of arsenism and in the process of carcinogenesis, and it may be one of the main reasons leading to its defect or deactivation of gene function.
下载:
