A quantitative morphometric study of the kinetics of tissue regeneration after administration of cisplatin

The effect of the anti-neoplastic drug cisplatin was investigated on several rat tissues using a novel computerized morphometric image analysis system. The rats were sacrificed in pre-determined intervals, ranging from 1 to 36 days after drug administration, and their liver, kidneys and external ears were sampled and sectioned. Tritiated thymidine was injected into each rat 1 h prior to sacrifice to enable autoradiographical explorations. All sections were histomorphometrically studied by a computerized system. The kidneys of the experimental group revealed increased tubular diameters, especially in the corticomedullar region. In the ears, decreases of the mean epithelial thickness, in the mean number of nuclei and in the mean nuclear surface were observed. The thickness of the connective tissue also decreased significantly by the end of the first week and returned to its normal size later on. No changes were detected in the ear cartilage. In the liver, no morphometrical differences were noticed in the hepatocyte density, Kupffer cell density or nuclear area. The nuclei of the hepatocytes and Kupffer cells retained a constant ratio to the total number of cells throughout the whole experiment. Liver autoradiography revealed that the hepatocyte and Kupffer cell labeling indexes after cisplatin administration were significantly higher than those of the control group, indicating enhanced replication of cells and increased synthesis of DNA, which in turn is accumulated in the nuclei and turn the cells into polyploids. In addition, the mean radius of the liver acini after cisplatin was diminished, followed by a significant reduction in the size of the progenitor compartment. It is concluded that while the kidneys are the organs most affected by cisplatin, the progenitor compartment of the liver is heavily affected as well. Computerized morphometry was demonstrated as a highly reproducible and accurate quantitative method for evaluation of histopathological changes in various mammalian tissues.