中文摘要：

目的 探讨燃煤砷污染对人体p53基因甲基化（启动子区及第5外显子）和突变（第5外显子）的影响,分析其与燃煤型砷中毒的关系.方法 在贵州省兴仁县燃煤型砷中毒病区选择112例砷中毒患者,根据病情将其分为轻度中毒组（38例）、中度中毒组（43例）和重度中毒组（31例）;根据有皮肤病理学诊断患者（43例）的病理结果,将其分为非癌变组（24例）和癌变组（19例）.选择条件相似的非砷暴露村90名居民作为对照组.在知情同意原则下,采集上述观察对象的外周血,应用限制性内切酶-PCR法检测p53基因启动子区及第5外显子甲基化情况,应用PCR-单链构象多态性技术及PCR产物克隆测序技术检测p53基因第5外显子突变情况.结果 p53基因启动子区甲基化阳性率在轻、中、重度组分别为13.16%（5/38）、27.91%（12/43）、45.16%（14/31）,与对照组[1.11%（1/90）]比较差异均有统计学意义（χ2值分别为8.679、23.690、41.199,P值均＜0.017）;在非癌变组和癌变组分别为25.00%（6/24）和63.16%（12/19）,与对照组[1.11%（1/90）]比较差异均有统计学意义（χ2值分别为18.762、57.497,P值均＜0.025）.p53基因第5外显子甲基化阳性率在轻、中、重度组分别为55.26%（21/38）、51.16%（22/43）、48.39%（15/31）,与对照组[88.88%（80/90）]比较差异有统计学意义（χ2值分别为18.151、23.168、22.420,P值均＜0.017）;在非癌变组和癌变组分别为54.17%（13/24）和42.11%（8/19）,与对照组[88.88%（80/90）]比较差异有统计学意义（χ2值分别为15.201、22.075,P值均＜0.025）.p53基因第5外显子突变率在轻、中、重度组分别为5.26%（2/38）、16.28%（7/43）、25.81%（8/31）,中、重度组与对照组（0.00%）比较差异均有统计学意义（χ2值分别为15.465、24.870,P值均＜0.017）;在非癌变组和癌变组分别为16.67%（4/24）、31.58%（6/19）,与对照组（0.00%）比较差异均有统?

英文摘要：

Objective To explore the influence of arsenic pollution caused by coal-burning on methylation（promoter and exon 5 ） and mutation （exon 5 ） of human p53 gene, and to analyze the relationship between methylation, mutation and arsenism. Methods According to the diagnostic criteria of endemic arsenism, 112 patients with arsenism （including 38 mild cases,43 moderate cases and 31 severe cases） were selected in the areas with endemic arsenism from Xingren, Guizhou province. Among the subjects ,43 cases were diagnosed by dermatopathological methods, and they were divided into non-cancerous group （24 cases） and cancerous group （ 19 cases ）. 90 controls were selected from the non-arsenic polluted areas. Under the principle of informed consent, blood samples were collected from individuals. The methylation of p53 gene in promoter region and exon 5 were detected by extinction enzyme-PCR,the mutation of p53 gene （exon 5 ） was detected by PCR-SSCP,PCR products cloning and sequencing technology. Results The positive rates of methylation of p53 gene in promoter region were 13. 16% （ 5/38 ）, 27.91% （ 12/43 ）and 45. 16% （14/31） respectively among mild, moderate and severe arsenism group, which were obviously higher than the rates in the control group （1.11% （1/90）, χ2 values were 8.679,23.690, 41. 199,respectively,both P values 〈 0. 017 ）. The positive rates of methylation of p53 gene were 25.00% （6/24）and 63. 16% （12/19）in non-cancerous and cancerous group respectively, which were obviously higher than those in the control group （ 1. 11% （1/90） ,χ2 values were 18. 762,57. 497,respectively,both P values 〈0. 025 ）. The positive rates of methylation of p53 gene （ exon 5 ） were 55.26% （ 21/38 ）, 51. 16% （ 22/43 ）and 48. 39% （15/31）respectively among mild, moderate and severe arsenism group,which were obviously lower than the rates in the control group （ 88. 88% （ 80/90 ）, χ2 values were 18. 151 , 23. 168,22. 420,respectively, both P values 〈 0.