A novel form of chronic, active hepatitis of unknown etiology was discovered in our mice, associated with a high incidence of hepatocellular tumors. After a helical microorganism was discovered in hepatic parenchyma of diseased mice, we undertook characterization of the organism and investigation of its relationship to the disease process. We transmitted the hepatitis with liver suspensions from affected mice and by inoculation with bacterial cultures. A new species of Helicobacter (provisionally designated Helicobacter hepaticus sp. nov.) that selectively and persistently colonizes the hepatic bile canaliculi of mice was identified. The novel Helicobacter is a likely candidate for the etiology of hepatocellular tumors in our mice. The Helicobacter- associated chronic active hepatitis represents a new model to study mechanisms of carcinogenesis by this genus of bacteria, another species of which, Helicobacter pylori, is associated with gastric adenocarcinoma. In a study of cell type of origin of promoted liver cancer, the fate of placental glutathione S-transferase (GST-P)-immunoreactive hepatocytes, detectable in livers of rats soon after treatment with N-nitrosodi- ethylamine (DEN), was examined sequentially with or without phenobarbital (PB) promotion. The results suggest that the promotive effect of PB is most evident as an increase in larger hepatocyte populations composed of more than three GST-P+ hepatocytes, rather than in increasing the populations of single GST-P immunoreactive cells. PB may cause clonal expansion of these single GST-P reactive hepatocytes. This study provides evidence for the hypothesis that some of the GST-P reactive hepatocytes are initiated cells. Tumor promotion may also contribute to development of kidney cancer. Sodium barbital (NaBB), a long-duration sedative/hypnotic barbiturate, is a nongenotoxic nephrotoxin and induces chronic persistent increases in rates of cell proliferation in renal cortical tubules of male rats. We obtained evidence based on comparative morphology and serial sectioning that NaBB may promote naturally- occurring renal preneoplastic or neoplastic tubular lesions of this unique phenotype.
