Adult rat liver contains a minor population of hepatocytes called small hepatocytes (SHs) that are smaller in size and show a higher replicative potential than conventional parenchymal hepatocytes (PHs). However, SHs have been hitherto characterized using a "SH-fraction" that was contaminated with PHs. In the present study, we isolated a PH-free SH-fraction from the adult rat liver using fluore...

Expression of the canalicular multispecific organic anion transporter (cMOAT), an efflux pump involved in biliary secretion of xenobiotics, was investigated in rat hepatocytes exposed to the chemopreventive agent oltipraz. Northern blotting indicated that this compound increased cMOAT mRNA levels in primary cultured hepatocytes. Such an induction of cMOAT transcripts was demonstrated to be dose...

BACKGROUND & AIMS Cholecystokinin (CCK) is a major gastrointestinal peptide hormone that is released postprandially from the small intestine and exerts marked effects on gallbladder and gastrointestinal motility. The smaller isoforms CCK-8 and CCK-4 are rapidly taken up into hepatocytes, metabolized, and excreted into bile. Our aim was to identify and characterize the hepatocellular CCK-8 uptak...

To optimize conditions for retroviral-mediated transfer of a recombinant gene to hepatocytes, the pMNSM-Tk-lacZ vector, which we had constructed to express the bacterial beta-galactosidase gene, was transduced to rat hepatocytes under various conditions, and the expression of beta-galactosidase activity was examined by cytochemical staining. Compared to the hepatocytes of adult rats, those of n...

Fotemustine is a clinically used DNA-alkylating 2-chloro-ethyl-substituted N-nitrosourea, which sometimes shows signs of haematotoxicity and reversible liver and renal toxicity as toxic side-effects. Mechanistic data on these side-effects are scarce and incomplete. In this study, firstly the cytotoxicity of fotemustine in freshly isolated rat hepatocytes was investigated and secondly the metabo...

Background: Combination of glycation and oxidation is associated with diabetes mellitus. The aim of this study was to clarify the effect of glycated proteins in presence of transition metal ions on production of reactive oxygen species (ROS) in rat hepatocyte suspension.  Methods: Glycated albumin was prepared by incubation of bovine serum albumin with 100 mM glucose in 0.3 M phosphate buffer a...

A method has been developed to assess the metabolism and mutagenic activation of carcinogens using human and rodent hepatocytes in vitro. A slicing technique which was especially useful for nonperfusable biopsy and resected surgical human liver tissue was used to prepare the hepatocytes. Metabolites of the model carcinogen 2-acetylaminofluorene (AAF) produced by human and rat hepatocytes were s...

We have investigated the effect of a therapeutic agent for liver disease, Laennec, on the GOT leakage from freshly isolated and primary cultured rat hepatocytes which were treated with CCl4. By treatment with Laennec together with CCl4, the GOT leakage from isolated hepatocytes increased and that from cultured hepatocytes decreased, compared to those incubated only with CCl4. The results sugges...

The LEC rat is an inbred mutant strain which spontaneously develops liver injury and subsequent liver cancer. Liver injury in LEC rats has recently been shown to be closely related to abnormal copper accumulation in the liver. Previously, we reported that LEC rat hepatocytes lose their growth potential, probably allowing selective growth of preneoplastic cells. In this study, to elucidate the e...

The metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant compound of the aminoimidazoazaarens (AIA) group of mutagens/carcinogens isolated from the crust of fried and broiled meat, was examined in freshly isolated hepatocytes from untreated rat, mouse, hamster, and guinea pig. Activation was evaluated by the total level of covalent binding of PhIP to macromole...