Durham S K, Brouwer A
Department of Toxicology and Pathology, Hoffmann-La Roche, Nutley, New Jersey 07110-1199.
Toxicol Pathol. 1989;17(4 Pt 2):782-8. doi: 10.1177/0192623389017004206.
Recent results (3) indicate that 200 mg 3,4,3',4'-tetrachlorobiphenyl induces hepatomegaly accompanied by significant decreases in serum and hepatic retinoid content and hepatocyte morphologic alterations of proliferated and vesiculated endoplasmic reticulum and megamitochondria with paracrystalline inclusions. There was also an associated change in the number, size, and distribution of lipid droplets in hepatocytes and fat-storing cells. Electron microscopic autoradiographic techniques were utilized to determine the cellular and subcellular distribution of 3H-3,4,3',4'-tetrachlorobiphenyl (3H-TCB) in the adult rat liver and determine if there is any relationship between subcellular morphologic change and radiolabel localization. Adult female WAG/Rij rats received a single intraperitoneal injection of 200 mg TCB/kg containing 1.85 mCi of 3H-TCB and were sacrificed at 1, 3, 7, and 14 days following exposure. The vast majority of 3H-TCB-derived radioactivity was located in the hepatocyte at all time points examined, ranging from 79-86% of the total number of autoradiographic grains counted over the liver cells. Sequential order of radiolabel localization per liver cell type at 1, 3, and 7 days was hepatocyte much greater than Kupffer cell greater than fat-storing cell greater than endothelial cell. At day 14, the sequential order of radiolabel localization per liver cell type was hepatocyte much greater than fat-storing cell greater than Kupffer cell greater than endothelial cell, which indicates that there was some shift movement of label over time. The lipid droplet, mitochondria, and endoplasmic reticulum were the subcellular structures or organelles of hepatocytes having the highest number of 3H-TCB-derived grains at all time periods examined.(ABSTRACT TRUNCATED AT 250 WORDS)
近期研究结果(3)表明,200毫克3,4,3',4'-四氯联苯可诱发肝脏肿大,同时血清和肝脏中的类视黄醇含量显著降低,肝细胞形态发生改变,出现内质网增生和空泡化以及含副晶状包涵体的巨型线粒体。肝细胞和贮脂细胞内脂滴的数量、大小和分布也发生了相应变化。利用电子显微镜放射自显影技术,确定了3H-3,4,3',4'-四氯联苯(3H-TCB)在成年大鼠肝脏中的细胞和亚细胞分布,并确定亚细胞形态变化与放射性标记定位之间是否存在任何关联。成年雌性WAG/Rij大鼠腹腔注射单次剂量为200毫克/千克的含1.85毫居里3H-TCB的TCB,并在接触后第1、3、7和14天处死。在所有检测时间点,绝大多数源自3H-TCB的放射性位于肝细胞内,占肝细胞上计数的放射自显影颗粒总数的79%-86%。在第1、3和7天,每种肝细胞类型的放射性标记定位顺序为:肝细胞远大于枯否细胞大于贮脂细胞大于内皮细胞。在第14天,每种肝细胞类型的放射性标记定位顺序为:肝细胞远大于贮脂细胞大于枯否细胞大于内皮细胞,这表明随着时间推移标记有一些转移运动。在所有检测时间段内,脂滴、线粒体和内质网是肝细胞内亚细胞结构或细胞器中3H-TCB衍生颗粒数量最多的。(摘要截断于250字)