Smolowitz R M, Hahn M E, Stegeman J J
Biology Department, Woods Hole Oceanographic Institution, MA 02543.
Drug Metab Dispos. 1991 Jan-Feb;19(1):113-23.
The regulation of different cytochrome P-450 forms and their functions in different organs and cell types could determine the susceptibility of those cells and organs to toxic effects of xenobiotics, including chemical carcinogenesis. Here we describe the cellular localization of cytochrome P-450E (P-450IA1) induced in 10 major organs or organ systems of a marine vertebrate species, the fish, Stenotomus chrysops (scup). Scup were injected ip with 3,3',4,4'-tetrachlorobiphenyl (TCB) at 1 mg/kg, or with 2,3,7,8-tetrachlorodibenzofuran (TCDF) at 3 micrograms/kg. Induction was verified by Western blot analysis of microsomes from selected organs (liver, kidney, and gill) using monoclonal antibody (MAb) 1-12-3 to scup P-450IA1. The localization of P-450IA1 was subsequently determined in sections prepared by standard histological methods (10% buffered formalin fixation, paraffin embedding), and stained with MAb 1-12-3 and peroxidase-labeled second antibody. P-450IA1 was induced in epithelial and endothelial cells in liver (including pancreatic tissue), kidney, gill, gut, spleen, testis, and ovary. Induction also was detected in endothelial cells, but not other types, in heart, brain, and red muscle. In heart, the staining was present in the endocardium as well as in the endothelium of the coronary vasculature and great vessels. Although TCDF and TCB both induced P-450IA1 in various cells of all organs examined, the effect of TCB was in most cases greater than that of TCDF. This may be due to a relatively higher TCB dosage. A wider staining distribution was seen in gut, gill, kidney, and gonad of TCB-treated fish, which might be explained by a greater penetration, or by excretion of parent TCB, as opposed to TCDF. In any case, the results show that these important environmental agents induce P-450IA1 in generally similar patterns in all organs examined. The common finding of a strong induction of P-450IA1 in endothelial cells in all organs examined supports the suggestion that the endothelium may be a primary site of P-450IA1 induction.
不同细胞色素P-450亚型的调控及其在不同器官和细胞类型中的功能，可能决定这些细胞和器官对包括化学致癌作用在内的外源化合物毒性作用的易感性。在此，我们描述了在一种海洋脊椎动物——鱼（条纹鲈）的10个主要器官或器官系统中诱导产生的细胞色素P-450E（P-450IA1）的细胞定位。给条纹鲈腹腔注射1 mg/kg的3,3',4,4'-四氯联苯（TCB）或3 μg/kg的2,3,7,8-四氯二苯并呋喃（TCDF）。使用针对条纹鲈P-450IA1的单克隆抗体（MAb）1-12-3，通过对选定器官（肝脏、肾脏和鳃）的微粒体进行蛋白质免疫印迹分析来验证诱导情况。随后，通过标准组织学方法（10%缓冲福尔马林固定、石蜡包埋）制备切片，并用MAb 1-12-3和过氧化物酶标记的二抗进行染色，确定P-450IA1的定位。在肝脏（包括胰腺组织）、肾脏、鳃、肠道、脾脏、睾丸和卵巢的上皮细胞和内皮细胞中诱导产生了P-450IA1。在心脏、大脑和红色肌肉的内皮细胞中也检测到了诱导，但在其他类型细胞中未检测到。在心脏中，染色出现在心内膜以及冠状血管和大血管的内皮中。尽管TCDF和TCB都在所有检查器官的各种细胞中诱导产生了P-450IA1，但在大多数情况下，TCB的作用大于TCDF。这可能是由于TCB剂量相对较高。在经TCB处理的鱼的肠道、鳃、肾脏和性腺中观察到更广泛的染色分布，这可能是由于其穿透性更强，或者与TCDF不同，TCB母体能够排泄。无论如何，结果表明这些重要的环境因子在所有检查器官中以大致相似的模式诱导产生P-450IA1。在所有检查器官的内皮细胞中均强烈诱导产生P-450IA1这一共同发现支持了内皮可能是P-450IA1诱导的主要部位这一观点。
