Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Solt-Farber resistant hepatocyte (RH) and Reddy (dietary peroxisome proliferator) hepatocarcinogenesis protocols were utilized to induce both preneoplastic and neoplastic nodules in male F-344 rats. Total cellular polypeptides from normal liver, ciprofibrate (CP)-induced and RH nodules were analyzed for both qualitative and quantitative changes using computer-assisted, high resolution two-dimensional polyacrylamide gel electrophoresis. Approximately 800-1000 cytosolic and 1000-1200 particulate polypeptides were readily separated and detected using an ultrasensitive silver stain. The two-dimensional polyacrylamide gel electrophoresis patterns were very similar for each tissue with respect to both the number of polypeptides detected and the overall patterns. Three cytosolic polypeptides, E, 6.90/47; F, 6.90/46; and G, 6.50/28 (designated pI/Mr X 10(-3], and two particulate polypeptides, B, 5.90/43; and D, 5.70/21; were detected in CP nodules but not in normal liver. Polypeptides B and D were also detected in RH nodules. No qualitative polypeptide differences were detected among the individual preneoplastic or individual neoplastic CP nodules or between preneoplastic and neoplastic CP nodules. Numerous quantitative changes in both known markers for hepatocarcinogenesis and in as yet unidentified polypeptides were noted. In RH nodules the Ya subunit of glutathione-S-transferase B (GST-B) and the Yb subunit of GST-A were increased 2-4-fold as compared to normal liver or in replicating liver following a 70% partial hepatectomy, while in CP nodules the Yb subunit was unaltered and the Ya subunit increased 4-fold as compared to normal. The Yp subunits of GST-P were increased from almost nondetectable levels in normal liver to one of the most abundant cytosolic polypeptides in RH nodules. In contrast, the Yp subunits were not detected in any of the CP nodules either on the two-dimensional polyacrylamide gel electrophoresis gels themselves or following Western transfer and immunoblot analysis with antibody against GST-P. Two additional polypeptide spots, which may represent Yc charge shift variants, appeared at the same molecular weight as the constitutively expressed Yc subunit of GST-B but shifted one charge unit each toward the acidic region in CP nodules. DT-diaphorase which was increased 2-3-fold in RH nodules was unaltered in CP nodules. In addition to these changes in known markers, 34 (22 cytosolic and 12 particulate) polypeptides were significantly increased while 27 (12 cytosolic and 15 particulate) polypeptides were decreased during CP-induced hepatocarcinogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Coordinate polypeptide expression during hepatocarcinogenesis in male F-344 rats: comparison of the Solt-Farber and Reddy models. 355 7

Using the Solt-Farber hepatocarcinogenesis model, a large population of preneoplastic and neoplastic nodules were induced in male Fischer 344 rats. Total cellular polypeptides from normal liver and individual preneoplastic and neoplastic nodules were analyzed for both qualitative and quantitative changes using computer assisted high resolution two-dimensional electrophoresis. Approximately 800-1000 cytosolic and 1200-1400 membrane associated polypeptides were readily separated and detected using an ultrasensitive silver stain. The polypeptide patterns were remarkably similar for each tissue and only four qualitative polypeptide differences were noted. One cytosolic polypeptide, 6.8/57 (designated pl/Mr X 10(-3), and three membrane associated polypeptides, 6.25/41, 6.75/24, and 6.05/21, were expressed in both preneoplastic and neoplastic nodules but not in normal liver. No qualitative polypeptide differences were detected among the individual preneoplastic or individual neoplastic nodules or between preneoplastic and neoplastic nodules. Numerous quantitative changes in both known markers for hepatocarcinogenesis and in as yet unidentified polypeptides were noted. In particular, the Ya subunit of glutathione S-transferase B, the Yb subunit of glutathione S-transferase A, as well as the three isoelectric point variants of the Yp subunit of glutathione S-transferase P were increased 2-, 4-, and 7-fold, respectively, in preneoplastic and neoplastic nodules. Whereas DT-diaphorase was increased 2-3-fold in hyperplastic nodules as compared to normal liver, no differences in the expression of albumin were noted. Although no differences were observed in the expression of aldehyde dehydrogenase in preneoplastic and neoplastic nodules, polypeptide b (6.9/54) was shifted slightly toward the basic region in normal liver. alpha-Fetoprotein was not detected in either preneoplastic or neoplastic nodules. In addition to these changes in known markers, comparison of 500-800 cytosolic and 750-1000 membrane associated polypeptides showed that roughly 4-10% of the polypeptides were undergoing quantitative changes of at least 4-fold during these stages of hepatocarcinogenesis. Thirty (10 cytosolic and 20 membrane) polypeptides were significantly down-regulated while 22 (7 cytosolic and 15 membrane) polypeptides were up-regulated in both preneoplastic and neoplastic nodules. In all cases the direction and magnitude of change were the same in both preneoplastic and neoplastic nodules with the exception of three polypeptides.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sequential analysis of chemically induced hepatoma development in rats by two dimensional electrophoresis. 394 Feb 6

Effects of oxidative stress induced by redox-enzyme modulation on the progression stage of hepatocarcinogenesis were examined by monitoring both hepatocyte injury and hepatocellular carcinoma development in F344 rats bearing preneoplastic liver nodules induced by the Cayama-Farber procedure. Redox-enzyme modulation, which included increased cytochrome P450 reductase activity induced by phenobarbital-Na (100 mg/kg, i.p. for 3 days), inhibition of DT-diaphorase by dicumarol (25 mg/kg, i.p.), depletion of glutathione by phorone (200 mg/kg, i.p.), supplementation with the Fe(III) sodium salt of EDTA (50 mg/kg, i.p.) and redox-cycling activation by menadione (50 mg/kg, i.g.), exerted no prominent hepatocyte injury within nodules but did cause slight injury in the surrounding hepatocytes in nodule-bearing rats. The same treatments induced severe hepatocyte injury in non-treated normal rats. Redox-enzyme modulation performed every other week for 33 weeks significantly reduced the number of hepatocellular carcinomas developing in nodule-bearing rats. These results indicate that preneoplastic nodules are resistant to the oxidative stress induction caused by redox-enzyme modulation treatment and that, despite toxic effects in surrounding hepatocytes, no progression pressure is exerted. Indeed, the treatment rather demonstrates an inhibitory effect of the evolution of the nodules into hepatocellular carcinomas.
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PMID:Effects of oxidative stress induced by redox-enzyme modulation on the progression stage of rat hepatocarcinogenesis. 842 75

The chemopreventive activity of methanolic extract of Apium graveolens seeds (celery seeds) has been investigated against Solt Farber protocol of hepatocarcinogenesis, oxidative stress and induction of positive foci of gamma-GT in the liver of Wistar rats. The prophylactic treatment of celery seeds extract protected dose dependently against diethylnitrosoamine (DEN)+2-acetylaminofluorine (AAF)+partial hepatectomy (PH) induced hepatocarcinogenesis and other related events such as induction of gamma-GT positive foci (P<0.001). 2-AAF administration in diet with PH in rats resulted in increased hepatic ornithine decarboxylase (ODC) activity and a consequent increase in the rate of DNA synthesis when compared to saline treated control group while pretreatment of rats with celery seeds extract resulted in inhibition of aforementioned parameters dose dependently. The augmentation of quinone reductase (QR), glutathione-S-transferase (GST) and serum gamma-glutamyl transpeptidase (GGT) activities; and depletion of the tissue GSH content after 2-AAF (i.p. injection) for five consecutive days was prevented with the administration of celery seed extract. On the basis of the above results it can be said that A. graveolens is a potent plant against experimentally induced hepatocarcinogenesis in Wistar rats.
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PMID:Inhibitory effect of celery seeds extract on chemically induced hepatocarcinogenesis: modulation of cell proliferation, metabolism and altered hepatic foci development. 1579 22