Standop Jens, Ulrich Alexis B, Schneider Matthias B, Büchler Markus W, Pour Parviz M
UNMC Eppley Research Institute, University of Nebraska Medical Center, Omaha 68198, USA.
Pancreatology. 2002;2(6):510-8. doi: 10.1159/000066093.
BACKGROUND/AIMS: Chronic pancreatitis and pancreatic cancer have been linked to the exposure of environmental chemicals (xenobiotics), which generally require metabolic activation to highly reactive toxic or carcinogenic intermediates. The primary enzyme system involved is made up of numerous cytochrome P450 mono-oxygenases (CYP). Glutathione S-transferases (GST) belong to the enzyme systems that catalyze the conjugation of the reactive intermediates produced by CYPs to less toxic or readily excretable metabolites. Because the majority of chronic pancreatitis and pancreatic cancers develop in the organ's head, we compared the expression of selected CYP and GST enzymes between the tissues deriving from the ventral anlage (head) and dorsal anlage (corpus, tail).
A total of 20 normal pancreatic tissue specimen from organ donors and early autopsy cases were processed immunohistochemically by using antibodies to CYP 1A1, 1A2, 2B6, 2C8/9/19, 2D6, 2E1, 3A1, 3A2 and 3A4, GST-alpha, GST-mu and GST-pi, and the NADPH cytochrome P450 oxido-reductase (NA-OR), the specificity of which has been verified in our previous study by Western blot and RT-PCR analyses.
In all pancreatic regions, most of the enzymes were expressed in islet cells. However, more islets in the head region expressed CYP 2B6, 2C8/9/19, 2E1 and the NA-OR, than those in the body and tail. Moreover, the expression of CYP 2B6 and 2E1 was restricted to the pancreatic polypeptide (PP) cells, and the concentration of CYP 3A1 and 3A4 was stronger in PP cells than in other islet cells. On the other hand, GST-mu and GST-pi were expressed primarily in islet cells of the body and tail.
The greater content of xenobiotic-metabolizing and carcinogen-activating CYP enzymes and a lower expression of detoxifying GST enzymes in the head of the pancreas could be one reason for the greater susceptibility of this region for inflammatory and malignant diseases.
背景/目的：慢性胰腺炎和胰腺癌与环境化学物质（外源性物质）的暴露有关，这些物质通常需要代谢激活才能形成高反应性的有毒或致癌中间体。主要涉及的酶系统由众多细胞色素P450单加氧酶（CYP）组成。谷胱甘肽S-转移酶（GST）属于催化CYP产生的反应性中间体与毒性较低或易于排泄的代谢物结合的酶系统。由于大多数慢性胰腺炎和胰腺癌发生在胰腺头部，我们比较了源自腹侧原基（头部）和背侧原基（体部、尾部）的组织中所选CYP和GST酶的表达。
使用针对CYP 1A1、1A2、2B6、2C8/9/19、2D6、2E1、3A1、3A2和3A4、GST-α、GST-μ和GST-π以及NADPH细胞色素P450氧化还原酶（NA-OR）的抗体，对来自器官捐献者和早期尸检病例的20个正常胰腺组织标本进行免疫组织化学处理，其特异性已在我们先前的研究中通过蛋白质印迹和逆转录-聚合酶链反应分析得到验证。
在所有胰腺区域，大多数酶在胰岛细胞中表达。然而，头部区域表达CYP 2B6、2C8/9/19、2E1和NA-OR的胰岛比体部和尾部的更多。此外，CYP 2B6和2E1的表达仅限于胰多肽（PP）细胞，并且PP细胞中CYP 3A1和3A4的浓度比其他胰岛细胞中的更强。另一方面，GST-μ和GST-π主要在体部和尾部的胰岛细胞中表达。
胰腺头部外源性物质代谢和致癌物激活CYP酶含量较高而解毒GST酶表达较低，可能是该区域对炎症和恶性疾病易感性较高的一个原因。
