Biology of Hepatocellular Neoplasia In the Mouse. I. Histogenesis of Safrole-Induced Hepatocellular Carcinoma 1.2.3.4

ABSTRACT-A sequential. histologic analysis of the livers of male BALB/c mice chronically fed the hepatocarcinogen safrole (4,000 ppm) was performed at 2, 4. 8, 16, 24, 36. 52, and 75 weeks. The transplantability of selected lesions to syngeneic hosts was also assessed. Histopathologic liver alterations at 2, 4. 8, and 16 weeks included hypertrophy of centrolobular hepato-cytes, oval cell proliferation. fatty change in periportal hepato-cytes, and atypical nuclei. At 24-75 weeks, foci of cellular altera-tion, including basophilic. acidophilic. and clear cell. were noted. At 36 and 52 weeks. hepatocellular adenomas occurred in 4 of 10 and 7 of 10 mice, respectively. At 75 weeks they occurred in 5 of 5 mice. Adenomas were larger than a lobule in diameter, compressed the adjacent parenchyma. and distorted the hepatic architecture. Individual adenomas were composed of a mixture of basophilic, acidophilic, clear, and lipid-laden cells, arranged in disorganized cords. one to three cells in thickness. None of the 10 adenomas tested grew upon subcutaneous transplantation into syngeneic hosts. Hepatocellular carcinomas (HPC) develope