XPD mRNA及蛋白表达与燃煤型砷中毒关系

Relationship between transcription and protein expression of XPD and endemic arsenism caused by coal-burning

目的检测燃煤型砷中毒患者血中着色性干皮病D组基因（XPD）mRNA和皮肤组织中蛋白表达。方法选择贵州省燃煤污染型砷中毒病区110例患者为病例组（依发砷含量分为0～、2～和4～μg/g 3组）,以非砷污染村36名健康居民为对照组,二乙氨基二硫代甲酸银（DDC-Ag）法检测发砷含量、实时荧光定量PCR检测血中XPDmRNA表达;利用自愿手术治疗的62例患者皮肤标本（依发砷含量分为0～、2～和4～μg/g 3组,依皮肤病理学诊断分为一般皮肤病变组、癌前病变组和癌变组）和13例正常皮肤标本,免疫组织化学法检测XPD蛋白表达。结果发砷0～、2～、4～μg/g组中XPD mRNA相对表达量分别为0.267 5（0.040 3～0.462 6）、0.100 7（0.020 7～0.300 5）和0.170 7（0.016 9～0.528 0）,均低于对照组0.759 3（0.398 2～0.968 7）（P〈0.05）;病例组患者皮肤组织中XPD蛋白表达均低于对照组,发砷2～、4～μg/g组与对照组比较差异有统计学意义（P〈0.05）;癌前病变和癌变组XPD蛋白表达均低于对照组,差异有统计学意义（P〈0.05）。结论燃煤砷污染可致人体XPD基因表达异常,可能通过影响XPD对受损DNA的解旋,继发性抑制DNA修复,促进砷中毒乃至皮肤癌的发生发展。

Objective To investigate the transcription and protein expression of xeroderma pigmentosum group D（XPD） gene in peripheral blood and skin tissue among endemic arsenism patients caused by coal-burning.Methods Totally 110 patients were chosen as case group in endemic arsenism area in Guizhou province and divided into 0-,2-,and 4-μg/g group based on their hair arsenic contents.Another 36 healthy residents were chosen as control group.The content of hair arsenic was detected with diethyl dithio-carbamate argentine（DDC-Ag） and the mRNA expression level of XPD was detected by real-time fluorescence quantitative PCR.At the same time,62 skin tissue samples were collected from the voluntary surgical treatment patients with endemic arsenism and were divided into general pathological changes,precancerous,and cancerous group according to pathological measures.Another 13 cases from nontumor patients were chosen as control group.Skin samples were collected to detect XPD protein with immunohistochemical method.Results The mRNA levels of XPD were 0.267 5（0.040 3-0.462 6）,0.100 7（0.020 7-0.300 5）,and 0.170 7（0.016 9-0.528 0）,respectively,among 0-,2-,and 4-μg/g group and were lower than that of the control group（0.759 3[0.398 2-0.968 7]） with statistical differences（P0.05 for all）.The XPD protein expression of the case was lower than that of the control.There were statistical differences between 2,4μg/g group and the control group in the protein expression.There were statistical differences between the precancerous,cancerous and the control group in the protein expression.Conclusion Arsenic from coal-burning may cause abnormal transcription and protein expression of XPD,which may inhibit DNA repair capacity through affecting damaged DNA unwinding and promote occurrence,development of arsenism and even skin carcinogenesis.