Histogenesis of Hyperplasia and Carcinomas of the Liver Arising around Central Veins in Mice Ingesting Chlorinated Hydrocarbons

Abstract

The development of hyperplastic and neoplastic lesions of parenchymal cells of the liver adjacent to central veins was observed in C3H mice ingesting the chlorinated hydrocarbons, dieldrin or aldrin, in the diet. Lesions could be followed from pericentral hyperplasia to areas of hyperplasia, nodules of hyperplasia, small hepatocellular carcinomas, and large well-developed carcinomas, occasionally with metastases. Sometimes pericentral hyperplasia was diffuse throughout most or all of one lobe of the liver. These hyperplastic cells collided to become one large nodule and also one large carcinoma. The carcinomas were well-differentiated or moderately well-differentiated and grew on transplantation to isologous hosts. Histologically, the hyperplastic cells adjacent to central veins were increased in size, frequently with double nuclei. Carcinoma cells varied in size and shape and were huge with large nuclei, prominent nucleoli, and eosinophilic cytoplasm. Similar hepatocellular carcinomas were seen previously with carbon tetrachloride, another organochlorine chemical.

Background pathology in BDF1 mice allowed to live out their life-span

“…The incidence of hepatocellular carcinomas was three times as great as that of hepatocellular adenomas in male BDFI mice allowed to live out their life-span, suggesting a shift from benign to malignant (Reuber, 1975;Frith & Ward, 1980). Malignant lymphoma was the most common neoplasm in our female BDF I mice.…”

Preneoplastic and Neoplastic Progression during Hepatocarcinogenesis in Mice Injected with Diethylnitrosamine in Infancy

“…On the contrary, cells of this type, with abundant cytoplasm often make up the majority of foci and nodules induced by chronic treatment with carcinogen (35-37). There is good reason to consider some of them as precursors of trabecular carcinomas, since they appear early (35,37) and are often found intermixed in nodules containing trabecular hepatocellular carcinomas (36). Also, in one report, they were found to have a rate of replication intermediate between normal hepatocytes and carcinoma cells and both they and the carcinoma cells acquired an oncofetal antigen associated with plasma membranes (37).…”

“…There is good reason to consider some of them as precursors of trabecular carcinomas, since they appear early (35,37) and are often found intermixed in nodules containing trabecular hepatocellular carcinomas (36). Also, in one report, they were found to have a rate of replication intermediate between normal hepatocytes and carcinoma cells and both they and the carcinoma cells acquired an oncofetal antigen associated with plasma membranes (37). Thus, for the present, we suggest that carcinogen-induced premalignant foci could have either type of staining characteristic.…”

Dieldrin–Induced Mallory Bodies in Hepatic Tumors of Mice of Different Strains

“…The MBs in nontumorous livers were confined to the central region of the hepatic lobule. This is noteworthy in that, although previous papers on the carcinogenicity of dieldrin did not mention MBs (18, [24][25][26][27], the hepatocellular carcinomas which developed were believed to arise in the centrilobular region (18,24). The site of origin of the hepatic tumors produced in this experiment was not determined, although the histologic appearance of the tumors was similar to that previously reported (18,(24)(25)(26)(27).…”