Morphology and metastatic nature of induced hepatic nodular lesions in C57BL x C3H F1 mice

The metastatic capabilities of well-defined nodular hepatic lesions induced by benzo(a)pyrene, ethylnitrosourea, benzidine.2HCl, and diethylnitrosamine were evaluated. Coded liver and lung tissues from 1264 treated C57BL/6J x C3HeB/FeJ F1 mice were assessed independently for the presence of primary nodular lesions and metastases, respectively. Primary lesions were classified according to their size, cell morphology, and growth patterns into hyperplastic, adenomatous, and trabecular nodules. None of the 126 mice bearing hyperplastic nodules had pulmonary metastases. Four of 291 (1.4%) mice with adenomatous nodular lesions showed metastases. In contrast, of the 733 mice bearing the trabecular type of nodular lesions alone or in combination with other lesions 266 (36%) showed pulmonary metastases. The pulmonary metastases were first detected in mice dying between 51 and 60 weeks of age (5%). This rate increased as a function of age at death, reaching an incidence of 51% in mice surviving more than 81 weeks. It was concluded that nodules showing trabecular and the more anaplastic solid sheet type of growths represented bona fide hepatocellular carcinomas in the mouse.