|
1979年台灣台中.彰化等地區所發生的多氯聯苯中毒事件受害人數達二千
人之多,是我國有記錄以來相當嚴重的一次公害,也是全世界多氯聯苯中毒
之重要特例.從過去的研究中發現多氯聯苯中毒者的肝生檢值及誘發肝中
cytochrome P-450IA2酵素皆比對照組來得高,這顯示肝臟可能由於多氯聯
苯的暴露使肝細胞遭受破壞或促使cytochrome P-450IA2酵素受激發.本研
究主要貢獻是提供肝代謝途徑影響人類對毒物與AhR基因多型性對肝之共
同影響.哺乳動物的芳香烴接受器(Ah receptor)是影響類似戴奧辛化合
物(包括多氯聯苯/多氯夫喃)生理效應的關鍵機轉.1995年Kaname 等人指
出日本人之AhR發現在exon 10 的位置其氨基酸序序列554處有一個鹼基的
改變,由guanine 被取代為adenine(G1662--A1662),如此導致氨基酸有野
生型Arg(AGA)與突變型的Lys(AAA).本篇研究採集台灣的油症中毒者(
Yucheng)之血液,分析AhR基因的多型性.我們在引子(primers)的設計上改
變一個鹼基後,以PCR(polymerase chain recation)技術,將DNA放大後,再
以限制酵素MseI切割,用此方法分辨個體基因多型性.研究結果並未發現油
症患者體內多氯聯苯濃度對肝的損害會因不同的AhR基因型而有所改變.所
以,以我們所分析的樣本族群,目前並無足夠的證據證實AhR基因中exon10
的condon554氨基酸間之差異會影響油症中毒者體內多氯聯苯/多氯夫喃濃
度與肝酵素活性之相關性.
In 1979, the rice oils used by Taiwanese patients with Yucheng
were contaminted with PCBs, and their heat -degraded products
PCDFs,and PCQs. In our previous studies, liver biochemistry
has been studied in 302 Yucheng subjects and 273controls who
HbsAg(-) and anti HCV(-) and a significantlyhigher percentage of
abnormal liver function(GPT) were found in Yucheng subjects
compared to their control and promotion of CYP1A2 activity was
demonstrated by caffeine breath testin Yucheng subjects.The
mammalian aromatic hydrocarbon receptor (AhR) is generally
considered the initial event necessary for the expression of the
dioxin-like activity of these compounds. In 1995 Kaname et al.
found polymorphic site in the coding region of the AhR gene in
the Japanese in exon 10, one base change of guanine by adenine
resultingin one amino acid replacement of Arg(AGA)by Lys(AAA) at
codon 554 wasshown. In this study, Ah receptor genotypic
assessment of polymorphicsites in DNA by polymerase chain
reaction(PCR) and restriction enzyme MseI technique.The effect
of human Ah receptor gene polymorphisms on the
associationbetween serum PCBs/PCDFs level and liver enzymes
activity,in the population studied, can not be explained by one
amino acids difference in exon 10 at codon 554 of the AhR gene.
|