miRNAs are involved in many physiologic and disease processes by virtue of degrading specific mRNAs or inhibiting their translation. miR-148a has been implicated in the control of tumor growth and cholesterol and triglyceride homeostasis using in vitro or in vivo gene expression- and silencing-based approaches. Here miR-148a knockout (KO) mice were used to investigate the intrinsic role of miR-...

The methyl-deficient model of endogenous hepatocarcinogenesis in rodents is unique in that dietary omission rather than the addition of chemical carcinogens leads to tumor formation. Thus, the biochemical and molecular events predisposing to cancer in this model result from chronic metabolic stress and provide an ideal model system to study progressive alterations that occur during carcinogenes...

Significant changes in aldehyde dehydrogenase (ALDH) activity occur during chemically induced rat hepatocarcinogenesis. We have developed a procedure for the histochemical localization of hepatic ALDH which has proven extremely useful as an additional probe for studying changes in this enzyme during hepatocarcinogenesis. Frozen sections of fresh tissue were stained for ALDH using either propion...

Specific biochemical changes occurring during hepatocarcinogenesis have been sought by many investigators. The development of multistage models for hepatocarcinogenesis in the rodent has renewed interest in such marker alterations in preneoplastic as well as neoplastic hepatocytes. Preneoplastic altered hepatic foci (AHF) exhibit specific histomorphologic changes as viewed with tinctorial stain...

Enzymatic sulfation of N-hydroxylated arylamines by mammalian hepatic cytosol sulfotransferases (AST; EC 2.8.2.1) is an important metabolic step which generates ultimate carcinogens. The metabolic activity of AST IV, the putative isozymic form of AST primarily responsible for catalyzing N-hydroxy-2-acetylaminofluorene sulfation, is modulated during 2-acetylaminofluorene (AAF)-induced rat hepato...

Cyp2e1 plays an important role in chemically induced hepatocarcinogenesis. Resveratrol (REV) is known to prevent diethylnitrosamine (DEN)-induced hepatocarcinogenesis, but its effects on this process induced by DEN and 2-acetylaminofluorene (2-AAF) and the role of Cyp2e1 remain unclear. In this study, glutathione S-transferase placental form (GST-P)-positive foci were used as a marker of hepato...

Enzymatic sulfation of A'-hydroxylated arylamines by mammalian hepatic cytosol sulfotransferases (AST; EC 2.8.2.1) is an important metabolic step which generates ultimate carcinogens. The metabolic activity of AST IV, the putative ¡sozymicform of AST primarily respon sible for catalyzing /V-hydroxy-2-acetylaminofIuorene sulfation, is mod ulated during 2-acetylaminofluorene (AAF)-induced rat he...

The incidence of hepatocellular carcinoma (HCC) is more prevalent in males than in females. 5a-Dihydrotestosterone is the most potent form of androgen and is converted from testosterone by 5a-reductase. The antitumor effect of a 5a-reductase inhibitor (FK143) was evaluated in a rat chemical hepatocarcinogenesis model (Solt-Farber). Male Fischer 344 rats were used in three groups: (a) control gr...