染料廠員工N-乙醯基轉移酵素基因型與泌尿上皮細胞週期指標之相關研究

聯苯胺 (Benzidine)是一種染料的主成份物質，有關染料暴露與膀胱癌間具有相關性的報告早在1895年即被提出，隨後動物實驗也證實聯苯胺的確能誘發膀胱癌。聯苯胺類染料進入人體之後，通常會還原成自由態的聯苯胺，進而增加致癌的可能性。根據以往的研究，帶某種特定的N-乙醯基轉移酵素 (NAT2)基因型，再加上本身有抽菸習慣者，其罹患膀胱癌的相對危險性將顯著地增加，因此推測受到NAT2基因調控之N-乙醯基轉移酵素第二型的代謝功能，會影響人體去除致癌物質之能力。本研究對某染料製造廠員工採集血液，測定其代謝易感性標記NAT2基因多形性，另以流式細胞儀測定其尿液檢體細胞週期值作為膀胱泌尿上皮細胞受損程度的參考，以探討在聯苯胺暴露之後不同NAT2基因型對發生泌尿上皮細胞週期值異常的影響。本研究結果顯示，NAT2 M1異合子變異對偶基因型與聯苯胺暴露對泌尿上皮細胞週期值異常的產生，具有統計上的顯著關係 (P<0.05)。抽菸習慣對於泌尿上皮細胞週期值異常的產生，有正相關；而夜尿習慣則是具有保護的作用。以模式分析進一步調整暴露程度與其他干擾因子後，仍可發現帶有NAT2 M1型變異對偶基因者，較容易發生泌尿上皮細胞週期值異常；而高暴露族群當中帶此基因者也較具危險性且呈統計上有意義的差異 (OR=4.9, 95%C.I.=1.0-24.3)。綜合以上結果，本研究發現NAT2 M1型變異對偶基因在聯苯胺暴露與泌尿上皮細胞週期值異常之間，確實具有相當程度的影響。

關鍵字

聯苯胺；膀胱癌；流式細胞儀； N-乙醯基轉移酵素

並列摘要

Benzidine is a major compositions of amine dyes. In 1895, the association between dye exposure and bladder cancer has been reported. Later, some animal toxicity studies confirmed that benzidine can induce bladder tumor. Several studies presented that individuals with some mutant alleles of N-acetyltransferase (NAT2) were at increased bladder cancer risk if they were smokers or if they had worked in some occupations related to aromatic amines. Our previous study have shown that patients with bladder cancer have highly abnormal DNA ploidy in their urothelial cells. Base on the previous study, this study was designed to investigate the influence of NAT2 genotype on abnormal DNA ploidy of urothelial cells in dye manufacturing workers. Peripheral blood lymphocytes were collected from each subject and genotyped for NAT2 by PCR-RFLP methods. Among subjects with NAT2 M1 mutant allele and high exposure level was significantly associated with an increased risk of urothelial cell cycle DNA ploidy abnormal. (OR=4.9,95%C.I.=1.0-24.3). This result supports that NAT2 M1 mutant allele modified the effect of occupational exposure on the development of urothelial cell cycle DNA ploidy abnormal in dye workers.

並列關鍵字

Benzidine ； Bladder cancer ； Flow Cytometry ； N-acetyltransferase

國際替代計量

染料廠員工N-乙醯基轉移酵素基因型與泌尿上皮細胞週期指標之相關研究

未授權

主題瀏覽