The previously established mouse model for hepatic silicosis and fibrosis was evaluated for TGF-beta mRNA and protein expression and for its progression to hepatocarcinogenesis. Mice that received intraperitoneal (i.p.) quartz and survived for more than 12 months, developed liver cell adenoma and carcinomas in addition to hepatic silicotic granulomas and fibrosis. The adenomas have cytoplasmic inclusion bodies (CIB) similar to those induced by other hepatocarcinogens. Similar to previous observations on quartz-induced pulmonary lesions, hepatic adenomas expressed TGF-beta1 LAP protein but liver cell carcinomas did not. Spatial and temporal patterns of expression of TGF-beta1, TGF-beta2, TGF- beta receptor type II mRNAs and TGF-beta1 proteins in the hepatic lesions (cirrhosis and carcinomas) were observed and compared with controls. The results suggest that TGF-betas may play a role in the pathogenesis of quartz-induced hepatic lesions. Methods were developed for the culture of hepatocytes from explants of livers obtained from mice 3 months after treatment with quartz. Crystalline silica showed a marked dose-dependent toxicity on cultured hepatocytes. The hepatocyte cell model and the mouse models for quartz-induced cirrhosis and liver carcinoma will be suitable for further studies of cytokines and gene alterations in hepatocarcinogenesis by particulate materials. The hamster model for quartz-induced fibrosis and cirrhosis was also established. Similar patterns of TGF-beta1 mRNA expression were observed as in the mouse model. The induction of hepatic fibrosis and cirrhosis in the mouse and hamster shows that the hamster and mouse livers are susceptible to quartz-induced fibrogenesis but their lungs show variable resistance to quartz-induced fibrogenesis compared to the rat. The species differences exhibited in the lungs of these rodents are in contrast to the hepatic tissue response and may be due to organ-specific factors rather than species-specific host factors. This is the first time that quartz-induced liver cell carcinoma has been experimentally produced in rodents. Clinical implications of this study relate to reported cases of patients with hepatic silicosis and fibrosis.