The histogenesis and mechanisms responsible for progression of hepatocellular adenomas into carcinomas are under investigation. We found that spontaneous or chemically-induced hepatocellular adenomas of mice progress through a series of atypias into carcinomas. These atypias were characterized by changes in cell size, pleomorphism, cytoplasmic tinctorial properties and the presence of a trabecular pattern. The proportion of adenomas with atypias varied with time and a second dose of carcinogen. Recent human studies have also shown carcinomas developing in adenomatous lesions. Ipomeanol, a cancer chemotherapeutic agent presently in human clinical trials, was found to produce cytotoxic effects on normal bronchioles and on chemically-induced lung tumors of bronchiolar origin in hamsters. The drug produced necrosis of normal epithelium and tumor cells. The possible chemotherapeutic effect of ipomeanol was investigated in this new novel in situ model. The origin of renal tumors of cortical tubule origin was investigated using computerized 3-dimensional image analysis. Reconstruction of focal proliferative lesions including dysplastic tubules, small adenomas and larger lesions, was performed. Step and renal section techniques of kidney sections were used. We found that dysplastic tubules were often connected to the smallest adenomas. Our studies provided evidence for the origin of renal tubular cell tumors from dysplastic tubules. In a comparative study of histiocytic sarcomas in mice and rats, we found that the mouse tumor cells express histiocytic antigens that could be detected by immunohistochemistry. Histiocytic sarcomas arising in mouse uterus, proposed by others to arise from Schwann cells, lack S-100, a Schwann cell marker and express Mac-2 and lysozyme, two histiocytic markers. This study is in agreement with earlier experiments which showed expression of mononuclear phagocyte antigens in tumor cells.
