Abstract
Analysis of cell proliferation in spontaneous proliferative lesions in the adrenal medulla of Fischer 344 rats used in 2-year carcinogenicity studies was performed by determination of labeling indices for proliferating cell nuclear antigen (PCNA), mitotic indices, and numbers of silver-stained nucleolar organizer regions (AgNORs). The lesions were morphologically classified into hyperplasia, welldifferentiated medullary tumor (WMT), atypical medullary tumor showing cellular pleomorphism and atypia (AMT), and malignant medullary tumor with invasion or metastasis (MMT) categories. The mean values for PCNA labeling index in hyperplasia, WMT, AMT, and MMT were 2.9, 4.4, 9.9, and 43.6, respectively, in all cases significantly increased as compared with those in the normal medulla (labeling index: 0.3). The mean mitotic indices were also significantly increased in MMT. The mean numbers of AgNORs per nucleus in the cells of normal medulla, hyperplasia, WMT, AMT, and MMT were 1.72, 2.07, 2.12, 2.33, and 3.39, respectively. All proliferative lesions again demonstrated significant increase as compared to normal medulla. The results thus revealed cell proliferative activities of spontaneous proliferative lesions of the rat adrenal medulla to exhibit a stepwise increase from normal medullary cells through WMT to MMT. Furthermore, the proliferative potential of AMT was higher than that of WMT, but very much lower than that of MMT with both approaches to assessment.
