染料廠員工細胞色素酵素基因型1A2、N-乙醯基轉移酵素基因型第I型與泌尿上皮細胞週期指標之相關研究

Association of Cytochrome P-450 1A2 and N-acetyltransferase I Polymorphism with the Urothelial Cell Cycle Index in Dye Workers

劉宇真(Liu Yu-Chen)

指導教授 ： 葉錦瑩

臺北醫學大學/公共衛生暨營養學院/公共衛生學研究所/碩士(2000年)

摘要

在癌變的過程中，個體先天的宿因及外來環境因素可能分別或共同作用於起始、促進或進展等階段。以往學界大部分只專注於環境因素的探討，然在相同環境暴露下人類卻顯現了對疾病的不同感受性。因此本研究的目的為探討這等與生俱來易感受因子，人與人之間的分子、酵素間的差異。 人體攝入芳香環胺類物質會增加膀胱癌發生的危險性已有許多流行病學資料證實。而過去台灣染料業曾大量使用染料製造過程中的中間物質聯苯胺（Benzidine），因此，本研究選定一家位於北部地區具有二十八年歷史的染料製造廠，以本國籍員工共207人作為研究對象。藉由聚合脢連鎖反應(Polymerase Chain Reaction)和限制片段長度多型性(Restriction Fragment Length Polymorphism)結果發現細胞色素酵素1A2(-2964 GaA)基因型之分佈頻率為W(G)：M(A) = 72.7%：27.3%，氮-乙醯基轉移酵素基因型第一型之分佈頻率為3：4：10 ：11= 23%：49%：27%：1.4%。我們希望經由分析業者細胞色素酵素1A2基因型、氮-乙醯基轉移酵素基因型第一型與尿液檢體細胞週期分佈結果作比對，以探討不同基因型對染料製造廠員工在聯苯胺暴露後發生分子及泌尿上皮細胞傷害上的影響。 本研究結果顯示帶有CYP1A2 W/W+NAT1 10/10基因型組合者其於抽煙或聯苯胺暴露下皆對泌尿細胞週期的異常具影響性，於抽煙暴露下尤其明顯，而夜尿習慣則是呈現顯著性的保護作用。以模式分析下，調整各干擾因子後仍可發現帶有CYP1A2 W/W+NAT1 10/10基因型組合者對泌尿細胞週期異常的影響，雖未達統計上顯著意義性，但仍可提供瞭解此二基因型於人體代謝芳香胺化學物質機制中所扮演的角色。

關鍵字

聯苯胺 ； 細胞色素酵素基因型1A2 ； N-乙醯基轉移酵素基因型第I型 ； 基因多型性 ； 泌尿上皮細胞週期指標

並列摘要

In the cancerization process, congenital factors and environmental factors may jointly or separately affect one into the phases of initiation, promotion and progression. Formerly, academic world just only to probe into the environment factors. But under the same exposure, human shows differential susceptibility to diseases. Therefore, our study aims to confer the variation of molecular and enzyme between man to man which inherited. There is a lot of epidemiology data supported that human being increases the probability getting bladder cancer when they were exposed to aromatic amines. In the past, Taiwan dyestuff industries used amounts of intermediate (Benzidine) in the manufacturing process. Consequently, a total of 207 workers in our study were sampled from a dyestuff manufacturing factory which established for 28 years and located at northern part of Taiwan. With the techniques of Polymerase Chain Reaction and Restriction Fragment Length Polymorphism, we discovered the genotype distribution of CYP1A2(-2964 G→A mutant) is W(G)：M(A) = 72.7%：27.3% and NAT1 is 3：4：10：11 = 23%：49%：27%：1.4%. By the way of comparing genotype and DNA ploidy of urothelial cells, we hope to investigate the association between susceptible factors and urothelial cell damage in dyestuff manufacturing workers. As a result of our study exhibit those who carries genotype of CYP1A2 W/W+NAT1 10/10 would influence the DNA ploidy of urothelial cells to become abnormal under the exposure of smoking or benzidine, especially obvious in smoking group. In the modeling analyses, we still found the influence of CYP1A2 W/W+NAT1 10/10 genotype on abnormal DNA ploidy of urothelial cells after adjusted by several confounders, although it is not statistically significant, it still offers us to realize the roles of CYP1A2 and NAT1 in the mechanism of human metabolize aromatic amines.

並列關鍵字

Benzidine ； CYP1A2 ； NAT1 ； Polymorphism ； Urothelial Cell Cycle Index

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