phosphorus-radioisotopes and Carcinoma--Hepatocellular

PCBs are carcinogens, but for many decades it was assumed that PCBs may not possess initiating activity. Initiation is a process that involves changes in the DNA sequence, often, but not exclusively produced through DNA adduction by a reactive compound or reactive oxygen species (ROS). DNA adducts can be detected by (32)P-postlabeling, a method that Dr. Ramesh Gupta co-developed and refined. Today these types of assays together with other mechanistic studies provide convincing evidence that specific PCB congeners can be biotransformed to genotoxic and therefore potentially initiating metabolites. This review will provide an overview of our current knowledge of PCBs' genotoxic potential and mechanism of action, emphasizing the contributions of Dr. Ramesh Gupta during his tenures at the Universities of Kentucky and Louisville.

Topics: Animals; Carcinogens; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; DNA Adducts; DNA Damage; Humans; Isotope Labeling; Liver Neoplasms; Mutation; Phosphorus Radioisotopes; Polychlorinated Biphenyls; Toxicity Tests

To evaluate the preventive effects of phosphorus-32 glass microspheres (P32-GMS) in the recurrence of massive hepatocellular carcinomas (HCCs) after tumor resection.. Twenty-nine patients with massive HCCs received local P32-GMS implantation after liver tumors were removed, while the other 38 patients with massive HCCs were not treated with P32-GMS after hepatectomies. The radioactivity of the blood, urine and liver were examined. The complications, HCC recurrence and overall survival rates in the patients were analyzed.. P32-GMS implanted in the liver did not cause systemic absorption of P32. There were no significant differences of postoperative complications between the patients with and without P32-GMS treatment. The short-term (six months and 1 year) and long-term (2, 3 and over 3 years) recurrence rates in patients who received P32-GMS radiotherapy were significantly decreased, and the overall survival rates in this group were significantly improved.. P32-GMS implantation in the liver can significantly decrease the postoperative recurrence and improve the overall survival in HCCs patients after hepatectomy. This therapy may provide an innovative method in prevention of HCC recurrence after operation.

Topics: Carcinoma, Hepatocellular; Combined Modality Therapy; Female; Glass; Hepatectomy; Humans; Liver Neoplasms; Male; Microspheres; Middle Aged; Neoplasm Recurrence, Local; Phosphorus Radioisotopes; Radiotherapy

In this early Phase II study, the authors investigated the efficacy of intratumoral injection of P-32 chromic phosphate in 17 patients with refractory solid tumors or solitary metastases in terms of response rates and overall survival.. Seventeen patients (median age, 60 years) with either cytostatic drug-resistant tumors or tumors known to be primarily chemotherapy-resistant were entered into the study. After sonographic determination of the tumor volume, P-32 chromic phosphate (74-555 MBq) was injected into the central part of the tumor under sonographic guidance. Follow-up investigations included serial scintigraphy, sonographic examinations, and hematologic studies.. Injection of P-32 chromic phosphate into refractory tumors resulted in remarkable regression. The median survival of all patients was 13 months (range, 8-25 months). The response rate was 71% (12 patients). A complete remission was seen in 7 patients (41%), and the rate of partial remissions was 29% (5 patients). However, 5 patients (30%) did not respond to the treatment. In one patient thrombocytopenia was observed, but no other side effects were apparent. Important pathologic and anatomic changes within the tumor tissue were demonstrated in solitary liver metastases of gastrointestinal malignancies excised in second-look operations. In all cases examined, formation of a cyst within the area of central activity, surrounded by a centrifugal necrotic ring and a marginal fibrotic structure, was found.. Lack of persistent systemic or local side effects, as well as noteworthy efficacy, are properties of this optimal regional treatment modality with P-32 chromic phosphate. This modality deserves consideration for further clinical trials.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Chromium Compounds; Digestive System Neoplasms; Drug Resistance, Neoplasm; Female; Head and Neck Neoplasms; Humans; Injections, Intralesional; Lung Neoplasms; Male; Middle Aged; Neoplasms; Phosphates; Phosphorus Radioisotopes; Survival Rate

In the past, we have clinically evaluated radiolabelled antibodies in Hodgkin's disease and hepatocellular cancer. Increased tumour pressure, reduced vascularity and poor diffusion has limited significant radiolabelled antibody tumour dose deposition. Using intratumoural infusion of macroaggregated albumin to blockade exiting vasculature followed by colloidal chromic 32Phosphorous, we have been able to achieve 75% to 100% tumour dose deposition by interstitial tumour infusion under computerised tomographic guidance. Phase I studies in a variety of solid tumours indicate extremely high doses may be achieved without toxicity (i.e. non-resectable pancreas 900,000 cGy to 1.7 million cGy) with tumour control and remission. This is a review of those studies and how the technique was applied.

Topics: Astrocytoma; Brachytherapy; Brain Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Small Cell; Chemoembolization, Therapeutic; Chromium; Colloids; Dexamethasone; Head and Neck Neoplasms; Hodgkin Disease; Humans; Injections, Intralesional; Liver Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Phosphorus Radioisotopes; Radiography, Interventional; Radioimmunotherapy; Radiotherapy Dosage; Remission Induction; Serum Albumin; Tomography, X-Ray Computed

The aim of this paper was to observe the metabolic mode of 32P at the level of sub-target nuclides.. Twenty-one cancer patients were locally injected with 32P-labelled glass microspheres and then observed to determine the equalization of 32P radionuclide metabolism in the tumor target. We imaged 3 sub-target regions of interest (ROI) 1/3 the size in both the anterior and posterior directions by bremsstrahlung single-photon emission computed tomography (SPECT) X-ray imaging. The radiation dose parameters of the beta rays including the initial dose rate, the effective half-life, and the effective half-life of the cumulative radiation dose were then calculated.. The radionuclide metabolism of the 21 complete tumor targets complied with the mono-compartmental model of index metabolism, but the level of tumor control did not correlate with radiation dose parameters. In contrast, the radionuclide metabolism of the 63 sub-targets did not comply with the mono-compartmental model. Instead, 32 sub-targets were better represented by bi-compartmental or tri-compartmental metabolic models. None of the remaining 31 sub-targets complied with index metabolism.. The complexity of the radiation dose at the sub-target level partially explains poor local tumor control. Future studies will be required to improve the expression of internal exposure to radiation dose parameters.

Topics: Adolescent; Adult; Aged; Carcinoma, Hepatocellular; Child; Female; Humans; Laryngeal Neoplasms; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Microspheres; Middle Aged; Neoplasms; Phosphorus Radioisotopes; Radiation Dosage; Rectal Neoplasms; Stomach Neoplasms; Tomography, Emission-Computed, Single-Photon; Young Adult

The objective of this study was to retrospectively evaluate the efficacy of a combination of (32)P-glass microsphere-mediated intra-arterial internal radiation and chemoembolization for the treatment of hepatocellular carcinoma.. Twenty-five consecutive patients with primary hepatocellular carcinoma referred for radiation therapy were treated with intra-arterial infusion of (32)P-glass microspheres followed by chemoembolization. beta-bremsstrahlung imaging was performed to monitor microsphere distribution. A partition model and a radiation dose equation were used for determination of radiation exposure in various tissues. Clinical response was evaluated using computed axial tomography scans.. The mean estimated absorption dose in tumor tissue was 137.42 +/- 56.69 Gy. A receiver operating characteristic curve was used to establish 90.65 Gy as the cutoff absorption dose with the best sensitivity and specificity for predicting response. The overall tumor response rate was 92%, while response in patients with radiation doses >90.65 Gy was 100%. Overall median patient survival was 15 months.. beta-bremsstrahlung imaging following intra-arterial infusion of (32)P-glass microspheres and chemoembolization incorporates effective treatment with convenient dosimetry monitoring and manageable adverse events using a single surgical procedure. This approach is a safe and effective method for ameliorating hepatocellular carcinoma.

Topics: Adult; Aged; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cohort Studies; Dose-Response Relationship, Radiation; Female; Humans; Infusions, Intra-Arterial; Kaplan-Meier Estimate; Liver Neoplasms; Male; Microspheres; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Phosphorus Radioisotopes; Radiography, Interventional; Radionuclide Imaging; Radiotherapy Dosage; Retrospective Studies; Risk Assessment; Survival Analysis; Tomography, X-Ray Computed

Betel quid chewing, which contributes high concentration of safrole in saliva, is a popular oral habit in Taiwan. Safrole is a documented rodent hepatocarcinogen, yet its hepatocarcinogenic potential in human is not known. Here, we used LC/ESI-ITMS(n) and LC/QTOF-MS confirmed safrole-dGMP as reference standard to detect the safrole-DNA adduct in hepatic tissues from HBsAg-/HCV-seronegative hepatocellular carcinoma patients by (32)P-postlabeling. We first synthesized and confirmed safrole-dGMP by LC/MS. Two isomeric safrole-dGMPs were characterized as N(2)-(trans-isosafrol-3'-yl) deoxyguanosine and N(2)-(safrol-1'-yl) deoxyguanosine. This technique was able to detect hepatic safrole-DNA adduct in mice that were treated with safrole but not sensitive enough to detect safrole-DNA adduct in human samples. Using the nuclease P1 version of the (32)P-postlabeling technique, we detected the presence of safrole-DNA adduct in two out of 28 hepatic tissues from hepatocellular carcinoma patients, and only these two patients had a history of betel quid chewing lasting more than 10 years. From co-chromatography with the mass confirmed safrole-dGMPs, this safrole-DNA adduct was identified as N(2)-(trans-isosafrol-3'-yl) deoxyguanosine. These results suggest that betel quid-containing safrole might be involved in the pathogenesis of hepatocellular carcinoma in human beings and LC/MS has the potential to identify DNA adducts in clinical samples.

Topics: Alcohol Drinking; Animals; Areca; Carcinoma, Hepatocellular; Chromatography, Liquid; DNA Adducts; Female; Humans; Injections, Intraperitoneal; Liver Neoplasms, Experimental; Male; Mass Spectrometry; Mastication; Mice; Mice, Inbred BALB C; Molecular Structure; Phosphorus Radioisotopes; Safrole; Smoking; Spectrometry, Mass, Electrospray Ionization; Taiwan; Time Factors

While potentially very useful, percutaneously delivered brachytherapy of inoperable intra-abdominal solid tumors faces significant technical challenges. This first-in-man study is designed to determine the safety profile and therapeutic efficacy of a novel phosphorous (32P) brachytherapy device (BrachySil) in patients with unresectable hepatocellular carcinoma.. Patients received single percutaneous and transperitoneal implantations of BrachySil under local anesthesia directly into liver tumors under ultrasound or computed tomographic guidance, at an activity level of 4 MBq/cc of tumor. Toxicity was assessed by the nature, incidence, and severity of adverse events (Common Toxicity Criteria scores) and by hematology and clinical chemistry parameters. Target tumor response was assessed with computed tomographic scans at 12 and 24 weeks postimplantation using World Health Organization criteria.. Implantations were successfully carried out in 8 patients (13-74 MBq, mean 40 MBq per tumor) awake and under local anesthesia. Six of the 8 patients reported 19 adverse events, but no serious events were attributable to the study device. Changes in hematology and clinical chemistry were similarly minimal and reflected progressive underlying hepatic disease. All targeted tumors were responding at 12 weeks, with complete response (100% regression) in three lesions. At the end of the study, there were two complete responses, two partial responses, three stable diseases, and one progressive disease.. Percutaneous implantation of this novel 32P brachytherapy device into hepatocellular carcinoma is safe and well tolerated. A significant degree of antitumor efficacy was demonstrated at this low dose that warrants further investigation.

Topics: Aged; Aged, 80 and over; Brachytherapy; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Middle Aged; Phosphorus Radioisotopes; Radiography, Interventional; Radiotherapy Dosage; Silicon Compounds; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Interventional

3-Nitrobenzanthrone (3-nitro-7H-benz[d,e]anthracen-7-one, 3-NBA) is a powerful mutagen and a suspected human carcinogen existing in diesel exhaust and airborne particulates. Recently, one of the major presumed metabolites of 3-NBA, 3-aminobenzanthrone (3-ABA), was detected in human urine samples. Here we analyzed DNA adducts formed in 3-NBA-exposed human hepatoma HepG2 cells by a (32)P-postlabeling/thin layer chromatography (TLC) method and a (32)P-postlabeling/polyacrylamide gel electrophoresis (PAGE) method. With HepG2 cells exposed to 3-NBA (0.36-36.4 microM) for 3h, we obtained three spots or bands corresponding to adducted nucleotides. Two were assigned as 2-(2'-deoxyadenosin-N(6)-yl)-3-aminobenzanthrone-3'-phosphate (dA3'p-N(6)-C2-ABA) and 2-(2'-deoxyguanosin-N(2)-yl)-3-aminobenzanthrone-3'-phosphate (dG3'p-N(2)-C2-ABA), with identical mobilities to those of synthetic standards on PAGE analysis. The chemical structure of the substance corresponding to the other spot or band could not be identified. Quantitative analyses revealed that the major adduct was dA3'p-N(6)-C2-ABA and its relative adduct labeling (RAL) value at 36.4 microM of 3-NBA was 200.8+/-86.1/10(8)nucleotide.

Topics: Benz(a)Anthracenes; Carcinoma, Hepatocellular; Cell Line, Tumor; Chromatography, Thin Layer; DNA Adducts; Electrophoresis, Polyacrylamide Gel; Humans; Liver Neoplasms; Phosphorus Radioisotopes

A dramatic overexpression of IGFBP-1 is responsible for growth inhibition, in response to a low-protein diet feeding. It has been demonstrated that a fall in the amino acid concentration was directly responsible for IGFBP-1 induction. In this report, we sought to determine the mechanism by which amino acid limitation upregulates IGFBP-1 expression. Our results show that both transcriptional activation and mRNA stabilization are involved. We also demonstrate that (i) the mGCN2/ATF4 pathway is not involved in this regulation and (ii) the 3'UTR of IGFBP-1 mRNA is responsible for its destabilization and regulates its stability in response to amino acid starvation.

Topics: 3' Untranslated Regions; Amino Acids; Carcinoma, Hepatocellular; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Proteins; Leucine; Phosphorus Radioisotopes; Pregnancy Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Transcription, Genetic; Transcriptional Activation; Transfection; Up-Regulation

32P BioSilicon is a new, implantable, radiological medical device that comprises particles of highly pure silicon encapsulating 32phosphorus (32P) for the treatment of unresectable solid tumors. Prior to administration, the device particles are suspended in a formulant which provides an even suspension of the intended dose for implantation. The primary objective of this animal trial study was to investigate the effects of intratumoral injection of 32)P BioSilicon on human hepatocellular (HepG2) and pancreatic carcinoma (2119) xenografts implanted in nude mice (BALB/c). A secondary objective was the histopathologic examination of the tumor foci and surrounding tissue during the study.. Cultured human carcinoma cells (HepG2 and 2119) were injected s.c. into the gluteal region of nude mice. When the implanted tumors were approximately 1 cm in diameter, 32P BioSilicon (0.5, 1.0, and 2.0 MBq) or formulant was injected into the tumors. Implanted tumor size was measured once a week for 10 weeks. At study termination, the tumor and surrounding normal tissue were collected and fixed in 10% formalin and processed for histopathologic analysis.. 32P BioSilicon produced a reduction in HepG2 tumor volume when compared with formulant control, and complete response was observed among tumors in the 1.0 and 2.0 MBq treatment groups after week 8. There was also significant reduction in 2119 tumor volume in all treated groups, with the complete response rate of 67% in the 2.0 MBq group.. 32P BioSilicon suppressed the growth of both human hepatocellular and pancreatic carcinoma xenografts implanted in nude mice and complete responses were also observed in tumors at higher radiation doses.

Topics: Animals; Brachytherapy; Carcinoma, Hepatocellular; Cell Line, Tumor; Dose-Response Relationship, Radiation; Humans; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Pancreatic Neoplasms; Phosphorus Radioisotopes; Silicon; Treatment Outcome; Xenograft Model Antitumor Assays

To study the effects of phosphorus-32 glass microspheres ((32)P-GMS) on human hepatocellular carcinoma in nude mice.. Human liver cancer cell line was implanted into the dorsal subcutaneous tissue of 40 BALB/c nude mice. Then the 40 tumor-bearing BALB/ c nude mice were allocated into treatment group (n=32) and control group (n=8). In the former group different doses of (32)P-GMS were injected into the tumor mass, while in the latter nonradioactive (31)P-GMS was injected into the tumor mass. The experimental animals were sacrificed on the 14th day. The ultrastructural changes of tumor in both treatment group and control group were studied with transmission electron microscopy (TEM) and stereology.. In treatment group, a lot of tumor cells were killed and the death rate of tumor cells was much higher (35-70%). Ultrastructurally, severe nuclear damage was observed in the death cells. The characteristics of apoptosis such as margination of heterochromatin was also found in some tumor cells. Besides, well differentiated tumor cells, degenerative tumor cells and some lymphocytes were seen. The skin and muscle adjacent to the tumor were normal. In control group, the tumor consisted of poorly differentiated tumor cells, in which there were only a few of dead cells(5%). Stereological analysis of ultrastructural morphology showed that Vv of nuclei (53.31+/-3.46) and Vv of nucleoli(20.40+/-1.84) in the control group were larger than those(30.21+/-3.52 and 10.96+/-2.52) in the treatment group respectively (P<0.01), and Vv of RER (3.21+/-0.54) and Vv of mitochondria (4.53+/-0.89) in the control group were smaller than those (8.67+/-1.25 and 7.12+/-0.95) in the treatment group respectively (P<0.01, 0.05). Sv of the membrane of microvilli and canaliculi (27.12 um(2)/100 um(3)+/-11.84 um(2)/100 um(3)) in the control group was smaller than that (78.81 um(2)/100 um(3)+/- 19.69 um(2)/100 um(3)) in the treatment group (P<0.01). But Vv of lipid particles (3.71+/-1.97) and Vv of vacuoles (5.72+/-1.58) were much larger than those (0.30+/-0.16 and 0.35+/-0.15) in the treatment group respectively (P<0.05, P<0.01).. The experimental results indicate that local administration of (32)P-GMS can produce obvious effect on liver cancer cells and the anticancer effect of (32)P-GMS is directly proportional to the dose administrated. Ultrastructural stereology can also show the effect of (32)P-GMS on the normalization of tumor cells, which is beneficial to the prognosis and treatment of patients. Moreover, local administration of (32)P-GMS is also safe.

Topics: Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Humans; Liver Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron; Microspheres; Microvilli; Mitochondria; Necrosis; Neoplasm Transplantation; Phosphorus Radioisotopes

Topics: Adult; Carcinoma, Hepatocellular; Combined Modality Therapy; Embolization, Therapeutic; Female; Hepatic Artery; Humans; Injections, Intra-Arterial; Liver Neoplasms; Male; Microspheres; Middle Aged; Phosphorus Radioisotopes

Topics: Animals; Biological Transport; Carcinoma, Hepatocellular; Deoxyribonucleotides; Glycoconjugates; Humans; Ligands; Liver Neoplasms; Male; Metabolic Clearance Rate; Mice; Oligodeoxyribonucleotides, Antisense; Phosphorus Radioisotopes; Radioisotope Dilution Technique; Sulfur Radioisotopes; Thionucleotides; Tissue Distribution; Tumor Cells, Cultured

To evaluate the relationship between effects and internal radiation of phosphorus-32 glass microspheres embolization therapy for liver cancer patients.. From 1994 to 1998, 44 patients with unresectable liver cancer received intra-arterial radio-embolization therapy using (32)P-GMS. Preoperative and postoperative function and energy level of the liver were tested by liver function test and arterial blood ketone body ratio (AKBR). CT, single photon emission computer tomography (SPECT), and AFP were used to judge the effect of the therapy; multivariate analysis was made.. In the moderate dose group, low incidence of complication, high tumor shrinking rate and AFP decreasing rate, and long-term survival rate were observed. In the larger dose group, high incidence of liver failure, high tumor shrinking rate and AFP decreasing rate, and long-term survival rate were also observed. In the low dose group, low incidence of complication, but low tumor shrinking rate and AFP decreasing rate and long-term survival rate were not observed.. The reasonable radiation doses for liver cancer patients may be about 30 Gy; if liver cirrhosis is serious, the doses can be reduced.

Topics: Adult; Aged; Brachytherapy; Carcinoma, Hepatocellular; Embolization, Therapeutic; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Microspheres; Middle Aged; Phosphorus Radioisotopes; Radiotherapy Dosage; Survival Rate

To investigate the efficacy of internal radiation of (32)P-glass microspheres ((32)P-GMS) in unresected hepatocellular carcinoma (HCC) via subcutaneous arterial port.. Hepatic arterial (99)technetium-macroaggregate albumin ((99)Tc-MAA) scanning via subcutaneous arterial port was undertaken to measure lung/liver shunting ratio and tumor/liver ratio. Hepatic arterial infusion of (32)P-GMS was performed in 17 cases of HCC with a dose from 1.11 to 1.30 GBq. Twenty cases of HCC undergoing hepatic arterial chemoembolization (HACE) in the same period served as controls group.. There was no treatment-related death in the 17 cases. In 7 of the 17 cases, AFP level and/or tumor size decreased by 50% after treatment, with a response rate of 64.7%. The median survival time was 5.5 months, and the 3-, 6-, 9-, 12-month survival rates were 94.1%, 44.1%, 31.0%, 24.4%, respectively. The therapeutic efficacy was better than that of HACE. The survival time was significantly longer in patients with T/N ratio >or= 2 than in those with T/N < 2 (P < 0.05).. Hepatic arterial infusion of (32)P-GMS is an alternative treatment for unresected HCC.

Topics: Adult; Aged; alpha-Fetoproteins; Carcinoma, Hepatocellular; Female; Follow-Up Studies; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male; Microspheres; Middle Aged; Phosphorus Radioisotopes; Survival Rate

Insulin binding to its receptor induces the phosphorylation of cytosolic substrates, insulin receptor substrate (IRS)-1 and IRS-2, which associate with several Src homology-2 domain-containing proteins. To identify unique IRS-1-binding proteins, we screened a human heart cDNA library with 32P-labeled recombinant IRS-1 and obtained two isoforms (epsilon and zeta) of the 14-3-3 protein family. 14-3-3 protein has been shown to associate with IRS-1 in L6 myotubes, HepG2 hepatoma cells, Chinese hamster ovary cells, and bovine brain tissue. IRS-2, a protein structurally similar to IRS-1, was also shown to form a complex with 14-3-3 protein using a baculovirus expression system. The amount of 14-3-3 protein associated with IRS-1 was not affected by insulin stimulation but was increased significantly by treatment with okadaic acid, a potent serine/threonine phosphatase inhibitor. Peptide inhibition experiments using phosphoserine-containing peptides of IRS-1 revealed that IRS-1 contains three putative binding sites for 14-3-3 protein (Ser-270, Ser-374, and Ser-641). Among these three, the motif around Ser-270 is located in the phosphotyrosine binding domain of IRS-1, which is responsible for the interaction with the insulin receptor. Indeed, a truncated mutant of IRS-1 consisting of only the phosphotyrosine binding domain retained the capacity to bind to 14-3-3 protein in vivo. Finally, the effect of 14-3-3 protein binding on the insulin-induced phosphorylation of IRS-1 was investigated. Phosphoamino acid analysis revealed that IRS-1 coimmunoprecipitated with anti-14-3-3 antibody to be weakly phosphorylated after insulin stimulation, on tyrosine as well as serine residues, compared with IRS-1 immunoprecipitated with anti-IRS-1 antibody. Thus, the association with 14-3-3 protein may play a role in the regulation of insulin sensitivity by interrupting the association between the insulin receptor and IRS-1.

Topics: 14-3-3 Proteins; Adenosine Triphosphate; Amino Acid Sequence; Animals; Binding Sites; Brain; Carcinoma, Hepatocellular; Cattle; Cell Line; CHO Cells; Cricetinae; Gene Library; Humans; Insulin; Insulin Receptor Substrate Proteins; Intracellular Signaling Peptides and Proteins; Liver Neoplasms; Mice; Molecular Sequence Data; Myocardium; Okadaic Acid; Phosphoproteins; Phosphorus Radioisotopes; Phosphotyrosine; Protein Biosynthesis; Proteins; Rats; Receptor, Insulin; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Spodoptera; Transfection; Tumor Cells, Cultured; Tyrosine 3-Monooxygenase

The phosphorus-32 glass microspheres(32P-GMS) is a new radioembolizer for cancer therapy. From March 1994 to April 1995, 24 patients with unresectable hepatocellular carcinoma and 3 patients with cavernous hemangioma received internal radiation treatment of 32P-GMS. The clinical results demonstrated that hepatic arterial instillation of 32P-GMS appeared to be safe and effective for hepatocellular carcinoma. There was no significant bone marrow or renal toxicity or liver to pulmonary bypass. A transient change of liver function and fever occurred in almost all patients. Significant liver toxicity and gastrointestinal tract reaction were seen when radiation dose > 50 Gy or microspheres > 3 g, and then various postoperative complications occurred.

Topics: Adult; Brachytherapy; Carcinoma, Hepatocellular; Embolization, Therapeutic; Female; Fever; Glass; Hemangioma, Cavernous; Hepatitis; Humans; Liver Neoplasms; Male; Microspheres; Middle Aged; Phosphorus Radioisotopes; Radiation Dosage

Rats were treated with low doses of the hepatocarcinogens dimethylnitrosamine or thioacetamide, and livers were examined 48 h later. These treatments are known to produce altered RNA compartmentation, wherein a class of repetitive RNA sequences normally restricted to the nucleus appears in the cytoplasm. Reverse transcription-PCR amplifications demonstrated that the sequences showing altered compartmentation consisted largely of a subfamily of the rodent B2 sequence family, the counterpart of human Alu sequences involved in retrotransposition. Northern blot analyses showed that these B2 sequences were found in cytoplasmic RNA as 170- to 360-nucleotide "sense" transcripts, and competition hybridization experiments established that B2 sequences represented most (if not all) of the sequences showing altered compartmentation. The major increase in B2 transcriptions in cytoplasmic RNA was not associated with any change in B2 transcription by RNA polymerase III. In situ hybridizations showed that the altered compartmentation of B2 sequences occurred in well-delineated foci within the rat liver; these foci consisted of a central region containing a prominent infiltrate of macrophages admixed with small hepatocytes and a peripheral region of histologically normal hepatocytes that showed evidence of oxidative damage. Altered compartmentation of B2 sequences may represent an important focal initiatory change in a subset of hepatocytes, whereas subsequent retrotranspositional events (associated with Alu-like sequences) could predispose initiated cell foci to alterations in promotion/progression phases.

Topics: Animals; Base Sequence; Blotting, Northern; Carcinogens; Carcinoma, Hepatocellular; Cell Compartmentation; Dimethylnitrosamine; In Situ Hybridization; Liver Neoplasms; Male; Molecular Sequence Data; Nucleic Acid Conformation; Phosphorus Radioisotopes; Rats; Rats, Sprague-Dawley; Repetitive Sequences, Nucleic Acid; RNA, Antisense; RNA, Messenger; Thioacetamide; Time Factors

We evaluated the efficacy and side effect of 32P-Labelled glass microspheres (32P-GMS) as a radioembolizer for patients with advanced hepatocellular carcinoma (HCC). 24 patients with unresectable HCC received internal radiation treatment of 32P-GMS. The tumor size varied from 3.6 to 18 cm. Hepatic arterial embolization was carried out through intraoperative or Seldinger's method. The mean absorbed radiation dose of the liver was 3250 rad (range from 1200 rad to 8000 rad). The radiation intensity within the tumor was 3.3 times stronger than in liver tissue. Not significant bone marrow renal toxicity was noted within 1 to 3 months. > 50% of tumor shrinkage was found in 17 cases, and < 50% of tumor reduction in 5 cases. The cumulative survival rate of 3, 6, 12, 18, 24 months was 92%, 75%, 54%, 33% and 29%. Hepatic arterial instillation of 32P-GMS appears to be safe and effective for unresectable HCC even with portal vein thrombosis.

Topics: Adult; Brachytherapy; Carcinoma, Hepatocellular; Embolization, Therapeutic; Female; Glass; Humans; Liver Neoplasms; Male; Microspheres; Middle Aged; Phosphorus Radioisotopes; Survival Rate

A phosphooligosaccharide has been proposed as a second messenger of insulin. It is believed to be structurally related to the carbohydrate moiety of phosphatidylinositol glycan anchors of many cell surface proteins. Herein we demonstrate that [32]phosphate in freshly isolated adipocytes and [3H]galactose in cultured hepatoma cells (H4IIE) labeled the same set of three different glycolipids. With all three, the radiolabel was made water soluble by phosphatidylinositol(glycan)-specific phospholipase C or D catalyzed hydrolysis. We isolated the three phospholipase C-released substances. One of them was susceptible to nitrous acid deamination, indicative of a hexosamine with a free amino group. This phosphooligosaccharide structure had an apparent molecular mass between tetra- and pentaglucose by gel filtration. By anion-exchange chromatography it was separated into two differently charged and interconvertible species. Adipocytes stimulated with insulin accumulated the nitrous acid sensitive phosphooligosaccharide: after stimulation the intracellular level of free phosphooligosaccharide increased threefold within 5 min, fell off during the next few minutes and then remained at a slightly elevated level. After insulin stimulation the intracellular concentration of free phosphooligosaccharide was > 1,000-fold higher than in the incubation medium. When prepared from rat livers on a preparative scale, the oligosaccharide was also found to exhibit insulinomimetic effects on protein phosphorylation of insulin target proteins in intact adipocytes. After subcellular fractionation of adipocytes the lipid-bound [32P]phosphooligosaccharide of the plasma membrane was found to be localized in plasma membrane domains apparently corresponding to caveolae. Lipid-bound [32P]phosphooligosaccharide was found also in the microsomal fraction.

Topics: Adipocytes; Animals; Autoradiography; Carcinoma, Hepatocellular; Cell Fractionation; Cell Membrane; Cells, Cultured; Cytosol; Galactose; Insulin; Oligosaccharides; Phosphates; Phosphatidylinositols; Phosphorus Radioisotopes; Phosphorylation; Polysaccharides; Rats; Rats, Sprague-Dawley; Subcellular Fractions; Tritium

DNA adduct formation in the liver, pancreas, kidneys and uterus in ethynylestradiol (EE)-induced carcinogenesis and the effect of tamoxifen (TAM) on DNA adduct formation were evaluated in female Wistar JCL rats using the 32P-postlabeling method. Hyperplastic nodules were noted in the liver of all rats 4 months after the first oral administration of 0.075 mg of EE, and hepatocellular carcinoma was detected in 8.1% of rats treated with EE for 12 months. DNA adducts increased in the liver for 4 months, reaching a level of 7.3 adducts/10(7) nucleotides and decreasing thereafter. Formation of DNA adducts was also noted in the pancreas and kidney, but the adduct levels were lower than those in the liver. TAM inhibited estrogen receptors (ER) in liver tissues and completely suppressed the development of hyperplastic nodules or hepatocellular carcinoma but did not affect DNA adduct formation in the liver. In this model, therefore, EE is considered to cause mutations of hepatocytes due to DNA adduct formation without mediation by ER and to induce initiated cells to develop into hepatocellular carcinoma in the presence of ER-mediated hormonal activities.

Topics: Animals; Autoradiography; Carcinoma, Hepatocellular; DNA, Neoplasm; Estrogens; Ethinyl Estradiol; Female; Liver; Liver Neoplasms, Experimental; Neoplasms, Hormone-Dependent; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains; Receptors, Estrogen; Tamoxifen

We examined the effect of alcohol ingestion on hepatocarcinogenesis induced by oral administration of synthetic female hormones, 0.075 mg of ethynylestradiol (EE) and 6.0 mg of norethindrone acetate (NA), every day for 12 months in female Wistar rats. Administration of 10% ethanol in drinking water for 5 days a week every week resulted in the development of hepatocellular carcinoma (HCC) in 38.4% of the hormone-treated rats at 12 months, which is approximately 5 times the incidence of HCC observed following EE and NA treatment alone. The number of hyperplastic nodules was significantly higher than the number observed in the case of EE and NA treatment alone after 4 months of the experimental period. The additional alcohol treatment also increased the value of unoccupied nuclear estrogen receptors (ERn) at months 6 and 8 of the experimental period, and increased the value of total ERn in the rat liver after 6 months of the experimental period. This indicates that additional alcohol treatment may increase occupied ERn (estrogen-ER complex) in the rat liver. A 32P-postlabeling analysis of liver DNA revealed that the maximum number of extra spots consisting of modified nucleotides induced by EE and NA appeared earlier when the additional alcohol treatment was imposed. Consequently, alcohol affects the hepatocarcinogenesis by EE and NA, promoting not only the change in kinetics of ER, but also DNA adduct formation induced by EE and NA in the rat liver.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Carcinoma, Hepatocellular; Cell Nucleus; Cytosol; DNA; Estradiol Congeners; Ethanol; Ethinyl Estradiol; Female; gamma-Glutamyltransferase; Liver; Liver Neoplasms, Experimental; Norethindrone; Norethindrone Acetate; Phosphorus Radioisotopes; Progestins; Rats; Rats, Inbred Strains; Receptors, Estrogen

The asialoglycoprotein (ASGP) receptor undergoes constitutive endocytosis through the coated pit/coated vesicle pathway in hepatocytes. Studies on HepG2 cells have shown that the receptor is phosphorylated at serine under control conditions and following protein kinase C stimulation. This study examined whether the ASGP receptor could also serve as a substrate for a tyrosine kinase in HepG2 cells. 32P labeling was performed in membrane preparations, in permeabilized cells at 4 degrees C, and in intact cells at 37 degrees C. The phosphorylated ASGP receptor was isolated by immunoprecipitation, hydrolyzed in 6 N HCl at 110 degrees C, and analyzed by two-dimensional high voltage electrophoresis. The receptor isolated from a membrane preparation incubated in vitro with [gamma-32P]ATP incorporated radiolabel predominantly (greater than 90%) into phosphotyrosine. ASGP receptor phosphorylation at both tyrosine and serine was detected in intact cells incubated with phosphatase inhibitors for 60 min at 37 degrees C. The presence of both phenylarsine oxide (20 microM) and sodium orthovanadate (200 microM) was required for tyrosine phosphorylation. Use of these inhibitors together resulted in a 16.4-fold increase in phosphorylation of the immunoprecipitated ASGP receptor, whereas phosphorylation of total HepG2 membrane proteins was not significantly augmented by this procedure. Selective proteolytic digestion of ASGP receptors in isolated vesicles demonstrated that the phosphorylation site identified in these studies is located at tyrosine 5 in the cytoplasmic tail.

Topics: Asialoglycoprotein Receptor; Carcinoma, Hepatocellular; Cell Line; Cell Membrane; Endocytosis; Humans; Kinetics; Liver Neoplasms; Peptide Mapping; Phosphorus Radioisotopes; Phosphorylation; Receptors, Immunologic; Tyrosine

Purified nucleolar DNA was markedly degraded at a concentration of 13 mug/ml by bleomycin A2; bleomycin concentrations 20-30 times greater were required to degrade nucleoplasmic DNA. Whole nuclear DNA was degraded to only a small extent at 13 mug/ml but was markedly degraded at higher bleomycin concentrations. Treatment of the various types of DNA with high concentrations of bleomycin A2 produced low molecular weight (approximately 6S) fragments that were no longer sensitive to degradation by bleomycin A2. Hybridization studies demonstrated a loss of ribosomal DNA sequences from nucleolar DNA treated with bleomycin A2 in vitro. Studies on RNA synthesis in Novikoff hepatoma ascites cells in vitro showed there was a decreased uptake of 32Pi into high molecular weight nuclear RNA in the presence of bleomycin A2. These results indicate that nucleolar function is inhibited by a direct effect of bleomycin A2 on nucleolar DNA.

Topics: Ascitic Fluid; Bleomycin; Carbon Radioisotopes; Carcinoma, Hepatocellular; Cell Nucleolus; Cell Nucleus; Centrifugation, Density Gradient; DNA, Neoplasm; Leucine; Liver Neoplasms; Neoplasms, Experimental; Nucleic Acid Denaturation; Nucleic Acid Hybridization; Phosphorus; Phosphorus Radioisotopes; RNA, Neoplasm; RNA, Ribosomal; Thymidine; Transcription, Genetic; Tritium; Uridine

The phosphorylating of the lysine-rich histone at various stages in the cell cycle has been studied. In rapidly dividing cell populations the lysine-rich histone is phosphorylated rapidly after synthesis and more slowly once bound to the chromosome. The half-life of hydrolysis of such interphase phosphorylation in 5 hr except during mitosis when the phosphata hydrolysis increases almost three-fold. During mitosis there is extensive phosphorylation at sites different from those phosphorylated during interphase and a smaller measure of sites common to both mitotic and interphase cells. The sites of mitotic phosphorylation are most critically distinguished from those phosphorylated in interphase by the rapidly hydrolysis of M-phase phosphohistone when the cells divide and enter the G1 phase of the cell cycle.

Topics: Autoradiography; Carcinoma, Hepatocellular; Cells, Cultured; Demecolcine; DNA, Neoplasm; Electrophoresis; Histones; Hydroxyurea; Liver Neoplasms; Lysine; Mitosis; Neoplasms, Experimental; Phosphates; Phosphoproteins; Phosphoric Monoester Hydrolases; Phosphorus Radioisotopes; Tritium

Rat ascites hepatoma cell DNA polymerases (EC 2.7.7.7), especially low molecular weight polymerase, could incorporate a significant amount of single nucleotide into acid-soluble products in the absence of the other three deoxynucleoside triphosphates when activated DNA was used as a template. This relaxed requirement for deoxynucleotides was not observed when poly[d(A-T).d(T-A)] was used as a template. Nearest-neighbour base analyses of the products formed in the presence of a single deoxynuclesode triphosphate revealed that the reaction is not of a terminal transferase-type but a very limited repair synthesis in which one or a few triphosphates are incorporated at numerous 3'-hydroxyl ends.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Carcinoma, Hepatocellular; Cells, Cultured; DNA; DNA Nucleotidyltransferases; DNA Repair; Liver Neoplasms; Methods; Molecular Weight; Nucleotides; Phosphorus Radioisotopes; Polynucleotides; Rats; Templates, Genetic

The capacity to effectively label tumor cell hostones using very short pulses of [3-H]acetate and [32-P]phosphate (1 to 10 min) has been developed. Four histone fractions F3, F2a1, F2a2, and F2b are extensively acetylated in short time periods. About 70% of the acetate accumulated on the histone during a short pulse is removed with a half-life of similar to 3 min. The rest of the metabolically active acetate is removed with a half-life of 30 to 40 min. Histones F2a1, F2a2, and F1 are acetylated at the NH2 terminus and this modification is metabolically stable. In short pulses, histones are labeled with 32-P in the order F2a2 greater than F1 greater than F3 greater than F2a1 greater than F2b. All fractions have a fairly rapid turnover time (t1/2 similar 20 to 40 min) except F1 phosphate which turns over some 5 times more slowly.

Topics: Acetates; Acetylation; Carcinoma, Hepatocellular; Cell Nucleus; Cells, Cultured; Cycloheximide; Histones; Liver Neoplasms; Neoplasms, Experimental; Phosphates; Phosphorus Radioisotopes; Tritium

A variety of 6- and 8-substituted analogs of cAMP (cyclic adenosine 3:5-monophosphate) have been tested for their ability to increase activity of tyrosine aminotransferase (EC 2.6.1.5) in cultured Reuber H35 hepatoma cells. Some analogs, particularly the 8-thio-substituted ones, produced effects approximately equivalent to those generated by N-6, O2'-dibutyryl cAMP. In contrast, cAMP and its O-2-monobutyryl derivative were relatively ineffective even at very high concentrations, whereas three other analogs actually depressed the activity of the aminotransferase. Changes in enzyme activity generated by the various analogs were paralleled closely by changes in the relative rate of aminotransferase synthesis. An excellent correlation was found to exist between the ability of any given analog to influence the activity of tyrosine aminotransferase and that of phosphoenolpyruvate carboxykinase (EC 4.1.1.32). A similar correlation was found to exist between the ability of various analogs to evelate the activity of these enzymes and to inhibit reversibly the growth of H35 cells. Only one of five inhibitors of cAMP phosphodiesterase activity tested produce any increase in aminotransferase activity when added alone. All of the 6- and 8-substituted analogs tested, including noniducers, stimulated f1 histone phosphorylation in crude rat liver extracts with approximately equal potencies. On the other hand, dibutyryl cAMP was only a weak activator of protein kinase in vitro, even though it is a potent enzyme inducer. A possible resolution of this apparent discrepancy has been provided by preliminary analyses of site-specific f1 histone phosphorylation in whole cells. Only compounds active as aminotransferase inducers are capable of stimulating phosphorylation of the serine-37 residue of endogenous f1 histone (3- to 10-fold).

Topics: Animals; Butyrates; Carbon Radioisotopes; Carcinoma, Hepatocellular; Cell Line; Cyclic AMP; Cyclic GMP; Enzyme Activation; Inosine Nucleotides; Kinetics; Liver Neoplasms; Neoplasms, Experimental; Nucleotides, Cyclic; Phosphodiesterase Inhibitors; Phosphoenolpyruvate Carboxykinase (GTP); Phosphorus Radioisotopes; Protein Kinases; Rats; Structure-Activity Relationship; Theophylline; Time Factors; Tritium; Tyrosine Transaminase

Topics: Alkaline Phosphatase; Animals; Carcinoma, Hepatocellular; Electrophoresis, Paper; Electrophoresis, Polyacrylamide Gel; Liver; Liver Neoplasms; Macromolecular Substances; Male; Neoplasms, Experimental; Organophosphorus Compounds; Phosphates; Phosphoproteins; Phosphorus Radioisotopes; Rats; Serine; Sodium Dodecyl Sulfate; Tyrosine Transaminase

Topics: Adenylyl Cyclases; Animals; Carcinoma, Hepatocellular; Dose-Response Relationship, Drug; Epinephrine; Fluorides; Glucagon; Iodine Radioisotopes; Liver; Liver Neoplasms; Male; Phosphorus Radioisotopes; Rats

Topics: Adenine Nucleotides; Animals; Base Sequence; Carcinoma, Hepatocellular; Chromatography, Gel; Electrophoresis, Starch Gel; Liver; Liver Neoplasms; Male; Neoplasms, Experimental; Phosphorus Radioisotopes; Polynucleotides; Polyribosomes; Rats; RNA, Neoplasm; RNA, Ribosomal; Sodium Dodecyl Sulfate

Topics: Animals; Base Sequence; Carcinoma, Hepatocellular; Cellulose; Chromatography, Ion Exchange; Chromatography, Paper; Cytosine Nucleotides; Electrophoresis; Electrophoresis, Paper; Hydrogen-Ion Concentration; Liver Neoplasms; Male; Neoplasms, Experimental; Phosphoric Diester Hydrolases; Phosphorus Radioisotopes; Polynucleotides; Pyrimidine Nucleotides; Rats; Ribonucleases; RNA, Ribosomal; Spleen; Uracil Nucleotides

Topics: Animals; Ascitic Fluid; Autoradiography; Base Sequence; Carcinoma, Hepatocellular; Chromatography, Ion Exchange; Coliphages; DNA Viruses; Electrophoresis, Polyacrylamide Gel; Hydrogen-Ion Concentration; Hydrolysis; Liver Neoplasms; Macromolecular Substances; Male; Neoplasms, Experimental; Nucleotides; Oligonucleotides; Pancreas; Phosphorus Radioisotopes; Polynucleotides; Pyrimidine Nucleotides; Rats; Ribonucleases; RNA, Neoplasm; RNA, Ribosomal

Topics: Adenosine Monophosphate; Animals; Carcinoma, Hepatocellular; Cell Nucleus; Chromatography, Ion Exchange; Cyclic GMP; Cytosine Nucleotides; Electrophoresis, Polyacrylamide Gel; Liver Neoplasms; Molecular Weight; Neoplasms, Experimental; Phosphorus Radioisotopes; Rats; Ribonucleotides; RNA; Uracil Nucleotides

Topics: Amino Acids; Animals; Ascitic Fluid; Autoradiography; Carcinoma, Hepatocellular; Cell Fractionation; Cell Nucleolus; Electrophoresis, Polyacrylamide Gel; Hydrogen-Ion Concentration; Liver Neoplasms; Male; Molecular Weight; Neoplasm Proteins; Neoplasms, Experimental; Organophosphorus Compounds; Peptide Fragments; Phosphates; Phosphoproteins; Phosphorus Radioisotopes; Pronase; Rats; Serine; Solubility; Threonine

Topics: Adenosine Triphosphatases; Animals; Ascitic Fluid; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Cell Fractionation; Dinitrophenols; Female; Hepatectomy; Leukemia L1210; Liver; Liver Neoplasms; Liver Regeneration; Male; Mice; Mitochondria, Liver; Neoplasms, Experimental; Oxidative Phosphorylation; Oxygen Consumption; Phosphates; Phosphorus Radioisotopes; Rats; Uncoupling Agents

Topics: Animals; Calcium; Carcinoma, Hepatocellular; Cell Fractionation; Cell Membrane; Lipoproteins; Liver; Liver Neoplasms; Magnesium; Neoplasms, Experimental; Phospholipids; Phosphorus Radioisotopes; Rats; RNA; RNA, Neoplasm

Topics: Base Sequence; Carcinoma, Hepatocellular; Cell Nucleolus; Chromatography, DEAE-Cellulose; Chromatography, Ion Exchange; Electrophoresis, Paper; Liver; Liver Neoplasms; Neoplasms, Experimental; Pancreas; Phosphorus Radioisotopes; Ribonucleases; Ribonucleotides; RNA; RNA, Ribosomal

Topics: Animals; Carbon Radioisotopes; Carcinoma, Hepatocellular; Cell Fractionation; Cell Nucleus; DNA, Neoplasm; Histones; Liver; Liver Neoplasms; Lysine; Male; Neoplasms, Experimental; Nucleoproteins; Phosphates; Phosphorus Radioisotopes; Radiation Effects; Rats; Rats, Inbred ACI; Thymidine; Time Factors

Topics: Animals; Carcinoma, Hepatocellular; Cell Nucleolus; Cell Nucleus; Centrifugation, Density Gradient; Electrophoresis, Polyacrylamide Gel; Liver Neoplasms; Neoplasms, Experimental; Nucleic Acid Hybridization; Phosphorus Radioisotopes; Rats; Ribonucleotides; RNA, Messenger; RNA, Neoplasm; RNA, Ribosomal; Spectrophotometry, Ultraviolet

Topics: Adenosine Triphosphate; Animals; Carcinoma, Hepatocellular; Cell Line; Cell-Free System; Chromatography, Thin Layer; Cyclic AMP; Cyclic GMP; Hot Temperature; Liver Neoplasms; Lymphoma; Pentosephosphates; Phosphorus Radioisotopes; Phosphotransferases; Protein Kinases; Rats; Ribose; Tritium

Topics: Adenosine Triphosphate; Animals; Carcinoma, Hepatocellular; Cell Fractionation; Cell Line; Chromatography, DEAE-Cellulose; Cyclic AMP; Cytoplasm; Cytosol; Dialysis; Drug Stability; Hydrogen-Ion Concentration; Liver; Liver Neoplasms; Male; Neoplasm Proteins; Neoplasms, Experimental; Phosphoric Diester Hydrolases; Phosphorus Radioisotopes; Protein Binding; Protein Kinases; Proteins; Rats; Tritium

Topics: Amoeba; Animals; Autoradiography; Carcinoma, Hepatocellular; Cell Line; Cell Nucleus; Chromatin; Cytoplasm; Dactinomycin; Densitometry; Electrophoresis, Polyacrylamide Gel; Liver Neoplasms; Molecular Weight; Phosphorus Radioisotopes; Rats; RNA; RNA, Neoplasm; Transcription, Genetic

Topics: Carcinoma, Hepatocellular; Cells, Cultured; Cycloheximide; DNA, Neoplasm; Enzyme Activation; Histones; Hydroxyurea; Kinetics; Liver Neoplasms; Lysine; Neoplasm Proteins; Neoplasms, Experimental; Phosphates; Phosphoric Monoester Hydrolases; Phosphorus Radioisotopes; Thymidine; Tritium

Topics: Animals; Base Sequence; Carcinoma, Hepatocellular; Centrifugation, Density Gradient; Chromatography, Ion Exchange; Chromatography, Paper; Electrophoresis, Paper; Electrophoresis, Polyacrylamide Gel; Hydrogen-Ion Concentration; Hydrolysis; Liver Neoplasms; Male; Molecular Weight; Neoplasms, Experimental; Pancreas; Phosphoric Diester Hydrolases; Phosphorus Radioisotopes; Rats; Ribonucleases; Ribonucleotides; Ribosomes; RNA, Neoplasm; RNA, Ribosomal; Snakes; Spleen; Time Factors; Venoms

Topics: Adenosine Triphosphate; Animals; Calcium; Carcinoma, Hepatocellular; Cell Nucleolus; Cobalt; Cyclic AMP; Electrophoresis, Disc; Electrophoresis, Polyacrylamide Gel; Hydrogen-Ion Concentration; Kinetics; Liver Neoplasms; Magnesium; Manganese; Neoplasm Proteins; Neoplasms, Experimental; Phosphoproteins; Phosphorus Radioisotopes; Protein Kinases; Rats; Solubility; Time Factors; Zinc

Topics: Animals; Base Sequence; Carcinoma, Hepatocellular; Cell Nucleus; Cellulose; Centrifugation, Density Gradient; Chromatography, DEAE-Cellulose; Chromatography, Ion Exchange; Chromatography, Paper; Electrophoresis; Electrophoresis, Paper; Electrophoresis, Polyacrylamide Gel; Liver Neoplasms; Neoplasms, Experimental; Oligonucleotides; Pancreas; Phosphorus Radioisotopes; Rats; Ribonucleases; Ribonucleotides; RNA, Neoplasm

Topics: Acetates; Animals; Ascites; Carcinoma, Hepatocellular; Cell Nucleolus; Centrifugation, Density Gradient; Deoxyribonucleases; Edetic Acid; Electrophoresis; Electrophoresis, Polyacrylamide Gel; Histocytochemistry; Kinetics; Liver Neoplasms; Magnesium; Male; Microscopy, Electron; Neoplasms, Experimental; Nucleotides; Pepsin A; Phosphates; Phosphorus Radioisotopes; Polyvinyls; Proteins; Rats; Ribonucleases; Ribosomes; RNA, Ribosomal; Sucrose

Topics: Animals; Base Sequence; Carcinoma, Hepatocellular; Cellulose; Chromatography, Ion Exchange; Chromatography, Paper; Drug Stability; Electrophoresis; Electrophoresis, Paper; Electrophoresis, Polyacrylamide Gel; Hydrogen-Ion Concentration; Liver Neoplasms; Molecular Weight; Neoplasms, Experimental; Oligonucleotides; Pancreas; Phosphorus Radioisotopes; Rats; Ribonucleases; Ribonucleotides; RNA, Neoplasm

Topics: Animals; Carcinoma, Hepatocellular; Cell Nucleolus; Cell Nucleus; Chromatin; Electrophoresis, Polyacrylamide Gel; Isotope Labeling; Liver Neoplasms; Neoplasm Proteins; Neoplasms, Experimental; Phosphoproteins; Phosphorus Radioisotopes; Rats; Ribosomes; Serine; Time Factors

Topics: Animals; Carcinoma, Hepatocellular; Cyclic AMP; Enzyme Activation; Isoelectric Focusing; Isoenzymes; Liver; Liver Neoplasms; Neoplasms, Experimental; Phosphorus Radioisotopes; Protein Kinases; Rats; Ultracentrifugation

Topics: Adenosine Triphosphate; Amino Acids; Animals; Ascitic Fluid; Carbon Radioisotopes; Carcinoma, Hepatocellular; Cell Nucleolus; Centrifugation, Density Gradient; Cytoplasm; Diphosphates; Hydroxamic Acids; Hydroxylamines; Liver Neoplasms; Neoplasm Proteins; Neoplasms, Experimental; Phosphates; Phosphorus Radioisotopes; Rats; RNA, Transfer; Transfer RNA Aminoacylation

Topics: Animals; Calcium; Carcinoma, Hepatocellular; Lanthanum; Leukemia, Experimental; Liver Neoplasms; Lymphoma, Non-Hodgkin; Magnesium; Melanoma; Mice; Neoplasms, Experimental; Phosphates; Phosphorus Radioisotopes; Sarcoma, Experimental; Sodium

Topics: Animals; Carcinoma, Hepatocellular; Cations, Divalent; Cations, Monovalent; Cell Nucleolus; Centrifugation, Density Gradient; Chromatography, Ion Exchange; Chromatography, Paper; Coliphages; Electrophoresis, Polyacrylamide Gel; Endonucleases; Hydrogen-Ion Concentration; Kinetics; Liver Neoplasms; Macromolecular Substances; Male; Molecular Weight; Neoplasms, Experimental; Nucleoproteins; Pancreas; Phosphorus Radioisotopes; Rats; Ribonucleases; RNA, Ribosomal; Spectrophotometry, Ultraviolet; Temperature

Topics: Animals; Carbon Radioisotopes; Carcinoma, Hepatocellular; Chromatography, Gel; Cytosol; Leucyl Aminopeptidase; Liver; Liver Neoplasms; Neoplasm Proteins; Neoplasms, Experimental; Phosphorus; Phosphorus Radioisotopes; Protein Binding; Proteins; Rats

Topics: Animals; Carcinoma, Hepatocellular; Liver; Liver Neoplasms; Male; Neoplasms, Experimental; Nucleic Acid Hybridization; Nucleotides; Oligonucleotides; Phosphorus Radioisotopes; Rats; RNA, Neoplasm; RNA, Ribosomal

Topics: Carcinoma, Hepatocellular; Cell Nucleus; Centrifugation, Density Gradient; Deoxyribonucleotides; Electrophoresis; Hot Temperature; Hydrogen-Ion Concentration; Liver Neoplasms; Neoplasms, Experimental; Nucleic Acid Conformation; Osmolar Concentration; Phosphorus Radioisotopes; RNA; RNA, Ribosomal; Sodium Chloride; Spectrophotometry, Ultraviolet; Temperature

Topics: Animals; Ascites; Carcinoma, Hepatocellular; Cell Membrane; Glycerophosphates; Liver; Liver Neoplasms; Lysophosphatidylcholines; Male; Molecular Weight; Neoplasms, Experimental; Nucleic Acids; Phosphatidylethanolamines; Phosphatidylinositols; Phospholipids; Phosphorus Radioisotopes; Rats; Sphingomyelins

Topics: Animals; Ascitic Fluid; Base Sequence; Carcinoma, Hepatocellular; Cell Nucleolus; Cell Nucleus; Cells, Cultured; Cellulose; Centrifugation, Density Gradient; Electrophoresis; Electrophoresis, Paper; Electrophoresis, Polyacrylamide Gel; Hydrogen-Ion Concentration; Liver Neoplasms; Male; Molecular Weight; Neoplasms, Experimental; Nucleic Acid Conformation; Oligonucleotides; Phosphorus Radioisotopes; Rats; Ribonucleotides; RNA; RNA, Ribosomal