Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The carcinogenic potential of triethanolamine was examined in F344 rats. Triethanolamine was dissolved in distilled water at levels of 0 (control), 1, and 2%, and groups of 50 males and 50 females were given these doses ad libitum as drinking water for 2 yr. The dose levels in females were reduced by half from wk 69, because of associated nephrotoxicity. A variety of tumors developed in all groups, including the control group, and all tumors observed were histologically similar to spontaneous tumors in this strain of rats. No statistically significant increase of the incidence of any tumor was observed in the treated groups of both sexes by the chi-square test. In this study, however, there was an increase in nephrotoxicity, which appeared to have an adverse effect on the life expectancy of the treated animals, especially of females. Therefore, an age-adjusted statistical analysis on incidences of main tumors or tumor groups of both sexes was also done by methods recommended by Peto et al. (1980). The result showed that a positive trend (p less than 0.05) was noted in the occurrence of hepatic tumors (neoplastic nodule/hepatocellular carcinoma) in males and of uterine endometrial sarcomas and renal-cell adenomas in females. These tumors, however, have been observed spontaneously in this strain of rats, and their incidences in the control group of the present study were lower than those of our historical controls. These results may indicate that a positive trend in the occurrence of these tumors is not attributable to triethanolamine administration. Increased incidence of renal tumors in the female high-dose group may have been connected with renal damage. Histological examination of renal damage observed in the treated groups, especially in the female high-dose group, revealed acceleration of so-called chronic nephropathy. In addition, mineralization of the renal papilla, nodular hyperplasia of the pelvic mucosa, and pyelonephritis with or without papillary necrosis were also observed. Thus, it is concluded that under these experimental conditions triethanolamine is not carcinogenic in F344 rats but is toxic to the kidneys.
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PMID:Lack of carcinogenicity of triethanolamine in F344 rats. 377 84

Promoting activities of sodium phenobarbital (PB) and sodium saccharin (SS), incorporated in a semisynthetic diet (AIN-76A), on 2-stage carcinogenesis initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) or N,N-dibutylnitrosamine (DBN) in male F344 rats were investigated. For the first 4 weeks of the experiment, weanling male Fischer rats were fed Wayne diet containing 0.2% FANFT or drinking water containing 0.005% DBN. The control rats were given the basal diet and normal drinking water. Beginning at the fifth week, the rats were given the AIN-76A diet or this diet containing 0.05 or 0.15% PB or 5% SS. The experiment was terminated at the end of 100 weeks. PB significantly increased the incidence of transitional cell carcinoma of the bladder of the rats that had been treated with FANFT (P = 0.027). PB also increased the incidence of bladder carcinoma of the rats that had been treated with DBN, but the increase was not significant (P = 0.081). SS in the AIN-76A diet increased the incidence of bladder carcinoma in the rats which had been treated with FANFT or DBN, but the increase was not significant (P = 0.059 and 0.327, respectively). Both high and low doses of PB, but not SS, significantly increased the incidence of hepatocellular carcinoma in the rats that had been treated with DBN. None of the control rats that had been fed the basal diet or the basal diet containing low or high PB or 5% SS developed either bladder or liver carcinoma. These results demonstrate that PB promotes urinary bladder carcinogenesis of rats initiated with FANFT but not with DBN. In contrast to incorporation in commercial rat chows, SS incorporated in the AIN-76A diet is very weak in promoting bladder carcinogenesis. On the other hand, PB, but not SS, promotes hepatocarcinogenesis initiated with DBN. Neither PB nor SS promoted DBN-induced carcinogenesis of esophagus or forestomach.
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PMID:Effect of sodium phenobarbital and sodium saccharin in AIN-76A diet on carcinogenesis initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide and N,N-dibutylnitrosamine in male F344 rats. 377 37

The association of nucleolar phosphoprotein C23 with preribosomal ribonucleoprotein (RNP) particles was examined in Novikoff hepatoma nucleoli. RNA was labeled with [3H]uridine for various times in cell suspensions, and RNP particles were extracted from isolated nucleoli and fractionated by sucrose gradient ultracentrifugation. The majority of protein C23 cosedimented with fractions containing rapidly labeled RNA (RL fraction). To determine whether there was a direct association of RNA with protein C23, the RL fraction was exposed to ultraviolet (UV) light (254 nm) for short periods of time. After 2 min of exposure there was a 50% decrease in C23 as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses, with no significant further decrease at longer times. When UV-treated fractions were subjected to phenol/chloroform extractions, as much as 30% of the labeled RNA was found in the phenol (protein) layer, indicating that RNA became cross-linked to protein. Similarly, there was an increase in protein C23 extracted into the water layer after irradiation. By SDS-PAGE analyses the cross-linked species migrated more slowly than protein C23, appearing as a smear detected either by [3H]uridine radioactivity or by anti-C23 antibody. With anti-C23 antibodies, up to 25% of the labeled RNA was precipitated from the RL fraction. Dot-blot hybridizations, using cloned rDNA fragments as probes, indicated that the RNA in the RL fraction and the immunoprecipitated RNA contained sequences from 18S and 28S ribosomal RNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association of protein C23 with rapidly labeled nucleolar RNA. 379 May 20

We have identified an unusual resonance at 16.5 ppm in the 31P NMR spectrum of a Morris (7777) hepatoma grown in the inguinal fossa of a Buffalo rat as myoinositol 1,2-(cyclic) phosphate. This compound has been observed in all of the 32 tumors examined as well as in cultured cells derived from the tumor, but it has not been observed in normal rat tissues. Its level in the aqueous phase of chloroform/methanol/water extracts of the tumor is 70 +/- 40 nmol/g, wet weight (n = 4). The presence of a breakdown product of phosphatidylinositol at such high levels in a fast growing tumor may provide an important clue for understanding the metabolic defect that results in the malignant growth of this tumor.
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PMID:Observation of myo-inositol 1,2-(cyclic) phosphate in a Morris hepatoma by 31P NMR. 379 28

A large proportion of the metabolites formed from benzo[a]pyrene (BP) in cell cultures from rodents, fish and humans result from conjugation of an oxidized metabolite of BP with sulfate, glucuronic acid or glutathione (GSH). To improve the analysis of these metabolites, a reversed-phase ion-pair h.p.l.c. system using a step gradient of methanol:tetrabutyl-ammonium bromide in ammonium formate buffer has been developed for the separation of these three classes of conjugates. This system separated 3-hydroxy-BP glucuronide and sulfate conjugates and resolved them from GSH conjugates of BP 4,5-oxide, 7,8-oxide and 7,8-diol-9,10-epoxide. Cultures of early passage Syrian hamster, Wistar rat and Sencar mouse embryo cells, a bluegill fry (BF-2) cell line and a human hepatoma cell line (HepG2) were exposed to [3H]BP for 24 h. Medium samples from each were extracted with chloroform: methanol:water, and the water-soluble metabolites were analyzed by ion-pair h.p.l.c. The largest peak of metabolites in the media from cell cultures from rodents and the bluegill fry cell line co-eluted with the glucuronic acid conjugate of 3-hydroxy-BP. These phenol-glucuronides represented 48-62% of the total water-soluble metabolites in the fish and rodent cell cultures. Treatment of this material with beta-glucuronidase released 3-hydroxy-BP and 9-hydroxy-BP in ratios from 3:4 to 13.3:1 in various cultures. Media from the bluegill fry cell line and the mouse embryo cell cultures also contained a peak of BP-diol glucuronides; treatment of these peaks with beta-glucuronidase released mainly BP-7,8-diol. In HepG2 cells, 40% of the water-soluble metabolites were identified as sulfate conjugates of 3-hydroxy-BP and 9-hydroxy-BP. No glucuronic acid conjugates of BP metabolites were detected in HepG2 cells. Only small amounts of the water-soluble metabolites from these cell cultures eluted in the same volumes as the synthetic GSH conjugate of BP-4,5-oxide, BP-7,8-oxide and BP-7,8-diol-9,10-oxide. These studies indicate that conjugation with glucuronic acid represents a major pathway of formation of water-soluble metabolites from BP in cells derived from a number of species and demonstrate the value of this ion-pair h.p.l.c. system for the analysis of conjugates formed from BP.
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PMID:Separation by ion-pair high-performance liquid chromatography of the glucuronide, sulfate and glutathione conjugates formed from benzo[a]pyrene in cell cultures from rodents, fish and humans. 380 96

Sodium bis-hemisuccinates of 7 beta- and 7 alpha-hydroxycholesterols are moderately water-soluble. They have been tested intraperitoneally against the murine Krebs-II carcinoma, grown as an ascitic tumour, and their action has been compared with that of usual chemotherapeutic drugs, cyclophosphamide, 5-fluoro-uracil, and methotrexate. The hydroxycholesterol derivatives show a faster and stronger activity (life prolongation), and lead to the complete disappearance of the tumour in about 1/3 of the cases, even with one single injection. Similar results have been obtained (on fewer cases) with two other experimental ascitic tumours, the S-180 sarcoma and the ZHC hepatoma. The mechanism of action is not known; it appears to be very different from that of the usual anti-cancer chemotherapeutic agents.
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PMID:[In vivo antitumor activity of hydrosoluble derivatives of 7-hydroxycholesterols]. 391 87

To study the effects of total-body hyperthermia (TBH) on metastases from malignant tumors, Lewis lung carcinoma (LLC)-bearing C57BL/6 mice and mouse ascites hepatoma 134-bearing C3H/He mice were immersed in a heated water bath. Rectal temperature was maintained for 30 min at 40 degrees C or 42 degrees C. After treatment, the incidence of lung metastasis was analyzed in LLC-inoculated mice, and the presence or absence of metastasis in affiliated lymph nodes was determined in mouse ascites hepatoma 134-inoculated mice. A significant inhibition in primary tumor growth in LLC- and mouse ascites hepatoma 134-bearing mice treated with 42 degrees C TBH was noted. The incidence of lung metastasis was increased from the control level of 1.6 +/- 0.63 (SD) to 2.4 +/- 0.98 in the 42 degrees C TBH (P less than 0.01) groups but not in the 40 degrees C TBH group. Metastasis to affiliated lymph nodes was similar for the controls and the 40 degrees C and 42 degrees C TBH groups. The increase in lung metastasis in LLC-treated mice subjected to 42 degrees C TBH could be prevented by the combined use of anticancer drugs such as cis-diamminedichloroplatinum(II) (1.0, 3.0 mg/kg) or mitomycin C (0.3, 1.0 mg/kg). Furthermore, the combined use of 42 degrees C TBH and anticancer drugs showed the inhibition of primary tumor growth to a greater degree than did 42 degrees C TBH alone or anticancer drugs alone. Since 42 degrees C TBH may induce tumor metastasis, especially hematogenous metastasis, it seems advisable to use anticancer drugs in combination with clinical thermal applications.
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PMID:Effects of total-body hyperthermia on metastases from experimental mouse tumors. 391 41

To study the effects of total-body hyperthermia (TBH) and local one (LH) on tumor metastases in animal experiments, heat was delivered to Lewis lung carcinoma (LLC)-bearing C57BL/6 mice and mouse ascites hepatoma-134 (MH-134)-bearing C3H/He mice, by water bath immersion systemically and locally. Rectal temperature in TBH was kept at 40 or 42 degrees C, while intratumor temperature in LH, at 40, 42, or 43 degrees C, respectively for 30 min. Also backgrounds of spread of lung metastasis of LLC in the case of TBH at 42 degrees C have been investigated as well as strategic preventive measures for it. The following results were obtained: The growth of primary LLC and MH-134 tumors was inhibited by TBH and LH at 42 degrees C and LH at 43 degrees C. The lung metastases of LLC increased by TBH at 42 degrees C. The lymph node metastases of MH-134 decreased by LH at 43 degrees C. The increase of lung metastases of LLC by 42 degrees C TBH occurred within 24hr after the session, presumably due to the increase in intravascular invasion of tumor cells and accelerated implantation of them according to histological changes of lungs. The observable tendency toward lung metastases continued for 48hr after treatment, coincidentally with distinctness in observation of histological changes. The increase mentioned above could be prevented by combined use of 42 degrees C TBH with anticancer drugs, as cis-diamminedichloroplatinum II or mitomycin-C. This combination resulted in further inhibition of tumor growth of primary LLC also, than non-combined 42 degrees C TBH. Considering the above facts, combined treatment of TBH with anticancer drugs is believed much valid clinically, in preventing metastases and making higher exertions of antitumor effects.
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PMID:[Experimental studies on effects of total-body and local hyperthermia on metastases in mice]. 392 May

These experiments were designed to determine the characteristics of lactic acid utilization and production in vivo in Jensen sarcoma and Morris hepatoma 7288CTC. Arteriovenous differences for lactic and pyruvic acids, glucose, and the ketone bodies were measured across "tissue-isolated" tumors growing in fed and fasted rats. Lactic acid was utilized (n = 18), produced (n = 24), or neither utilized nor produced (n = 1) by the tumors. Net tumor lactate production or utilization did not depend on the mean rate of glucose utilization which was the same in the lactate-utilizing and -producing tumors. For the lactic acid-utilizing tumors, the mean arterial whole blood lactate concentration entering the tumor was 3.47 +/- 0.39 mM, and the concentration in the tumor venous blood was 2.31 +/- 0.25 mM. For the lactic acid-producing tumors, the mean arterial lactic acid concentration was 1.29 +/- 0.10 mM, and the tumor venous blood concentration was 2.19 +/- 0.19 mM. Thus, both lactate-producing and lactate-utilizing tumors showed identical rates of glucose utilization and identical lactic acid concentrations in the venous blood leaving the tumors. Metabolite levels were also measured in tumors that were freeze clamped in situ immediately following collection of the arterial and tumor venous blood samples. The lactic acid content in the tumor mass (corrected for total tumor water) and the concentration in the tumor venous blood plasma were nearly identical, suggesting that the lactate concentrations in the tumor cells and tumor venous blood are at equilibrium. Transport of lactic acid between arterial plasma and tumor or between tumor and venous plasma was always down a concentration gradient; net lactate uptake and release in these tumors followed the law of mass action. High lactate concentrations were not observed in the Jensen sarcomas or in the venous blood leaving these tumors, and we were unable to confirm earlier studies indicating that Jensen sarcomas are consistently high net lactate producers in vivo.
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PMID:In vivo lactate production and utilization by Jensen sarcoma and Morris hepatoma 7288CTC. 394 Jun 35

A single dose of 15 mg/kg dimethylnitrosamine is an initiator of hepatic tumour formation in rats but does not produce tumours without further treatment. Subsequent promotion by Na phenobarbitone (1000 micrograms/ml drinking water) leads to 40% or more of the rats developing hepatocellular carcinoma. Four days of dietary treatment designed to produce a wave of DNA synthesis at the time of initiation leads to an even greater yield of tumours and nodules after promotion. This effect of phenobarbitone does not appear to be directly related to its ability to induce enzyme activity in the liver because lower doses of phenobarbitone (100 micrograms/ml or less) did not promote tumour development in spite of being adequate for the induction of cytochrome P-450 and associated enzyme activity. A similar incidence of hepatocellular carcinoma was found in both the groups given DMN and the top dose of Na phenobarbitone (1000 micrograms/ml) whether or not they had been given the dietary pretreatment. However, hyperplastic nodules were seen only in the diet pre-treated group. This is discussed in relation to the hypothesis that hyperplastic nodules are precursors of hepatic carcinoma.
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PMID:Dose-response relationship for phenobarbitone promotion of liver tumours initiated by single dose dimethylnitrosamine. 394 31


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