Morphogenesis of epithelial neoplasms induced in the rat kidney by dimethylnitrosamine.
Morphogenesis of epithelial neoplasms induced in the rat kidney by dimethylnitrosamine.
复制标题
二甲基亚硝胺诱导大鼠肾脏上皮肿瘤的形态发生。
作者：
G. Hard;W. H. Butler
从24小时到肾腺癌的发展，跟踪单次腹腔注射致癌剂量的二甲基亚硝胺后肾小管上皮细胞的连续变化。急性变化特别涉及近端小管的第一段，尽管在较高剂量下，肾小球旁边的远端小管也总是受到影响。急性改变包括形成脂滴和细胞质颗粒体，在受损上皮细胞下方积累颗粒和膜碎片，以及散发性细胞坏死。这些变化与整个皮质管间空间的细胞弥漫性增加相关，其中巨噬细胞是主要的细胞类型。随着上皮损伤的消退，弥漫性单核细胞反应也消退。急性期后，曲小管内的细胞核明显增大，数量增加，但其频率和随机分布表明，它们与肿瘤的发展无关。从6周开始，在靠近肾小球的小管内发现偶尔的增生性病变。电子显微镜检查显示，这种病变具有异常刷状缘形成和核仁，这是发育良好的腺癌的特征。还描述了由水合细胞组成的其他生长较慢的增殖性病变。结论：二甲基亚硝胺诱发的肾腺癌至少有一部分起源于近曲小管第一段。
The sequential changes in tubular epithelium following single i.p. injections of dimethylnitrosamine in carcinogenic doses were followed from 24 hr up to the development of renal adenocarcinomas. The acute changes involved, in particular, the first segment of the proximal tubules, although at higher doses the distal tubules next to glomeruli were also invariably affected. The acute alterations consisted of the formation of lipid droplets and cytosegresomes, the accumulation of granular and membranous debris beneath injured epithelial cells, and sporadic cell necrosis. These changes were associated with a diffuse increase of cells throughout the cortical intertubular space, of which macrophages were the predominant cell type. As the epithelial damage resolved, so did the diffuse mononuclear reaction. Following the acute stage, grossly enlarged nuclei within the convoluted tubules increased in numbers, but their frequency and random distribution suggested that they were unrelated to neoplastic development. From 6 weeks onwards, occasional proliferative lesions were found within tubules located next to glomeruli. Electron microscopic examination revealed that such lesions possessed abnormal brush border formation and nucleoli, which were characteristic features of well-developed adenocarcinomas. Other slower growing proliferative lesions, consisting of hydrated cells, were also described. It was concluded that at least some dimethylnitrosamine-induced renal adenocarcinomas take their origin from the first segment of proximal convoluted tubules.