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

A novel mutation of the p53 gene has been found in a rat hepatoma cell line, FAA-HTC1. This cell line carried two kinds of abnormal p53 transcripts; one lacked the exon 8 sequence, and the other had a single base substitution G to T which resulted in a new stop codon in exon 8. In the genomic DNA, this base substitution in exon 8 was present, indicating that both transcripts were transcribed from the mutated gene. No mutation was detected in its two flanking introns. In this cell line, the exon-deleted transcript seems to be generated by exon skipping due to an unknown mechanism other than splice site mutations.
 ...
PMID:Alternatively-spliced p53 mRNA in the FAA-HTC1 rat hepatoma cell line without the splice site mutations. 129 97

Indocyanine green (ICG) was injected into rat liver nodules induced by 2-acetylaminofluorene (2-AAF) via portal vein. The relationship between ICG staining and cell atypism of liver nodules was examined by means of histology and DNA flow cytometry. After 2-AAF administration, many small nodules appeared on the liver surface. All hyperplastic nodules were ICG stained until 10 weeks after the administration, but some nodules were not stained after 14 weeks. ICG-stained nodules histologically consisted of benign tissues and borderline lesions, and many of them showed "diploidy" in DNA cytometry. ICG-unstained nodules consisted of hepatocellular carcinoma (HCCs) and borderline lesions, and many of them showed "aneuploidy". In this way, it has been suggested that HCC could derive from hyperplastic nodules and that they might lose an ability to take up ICG in the process of hepatocarcinogenesis. Immunohistochemical staining for glutathione-S-transferase alpha (GST-alpha), a carrier protein of ICG in hepatocytes, was well correlated with ICG staining in the nodules, suggesting that the loss of ICG uptake in HCC was partly due to the decrease of GST-alpha. Moreover, the appearance of ICG unstained and aneuploid nodules was significantly inhibited in rats which were fed on diet containing Syosaiko-to after the administration of 2-AAF. Chemopreventive effect of Syo-saiko-to on hepatocarcinogenesis was identified.
 ...
PMID:Rat liver nodules induced by 2-acetylaminofluorene lose an ability to take up indocyanine green in the process of hepatocarcinogenesis. 137 11

A rat tumour (MC7 sarcoma), growing subcutaneously, has been shown to be sensitive to a single application of flavone acetic acid. Thirteen rats were still alive after 50 days and 8 of these were tumour free, as compared with control rats which survived for 15.7 +/- 2.53 days. The 8 tumour free animals were rechallenged with MC7 sarcoma 40 weeks later, without further FAA treatment. The tumour grew initially but in all cases the animals became tumour free within 24 days. After a further 30 days they were rechallenged with D23 hepatoma which grew as effectively as in the controls.
 ...
PMID:Long-term effects of flavone acetic acid on the growth of a rat tumour. 150 21

With RNA-DNA hybridization techniques, the mRNA expression of c-Ha-ras, c-Ki-ras, N-ras, and c-fos oncogenes in rat liver with neoplastic nodules or hepatocellular carcinoma induced by DENA was found to be higher than that in normal liver. No significant difference of c-myc expression was observed between normal liver and liver with neoplastic nodules or hepatocellular carcinoma. In the initiation stage of hepatocarcinogenesis in DENA+AAF+PH+PB and AAF+PH+PB model systems, the expression of c-myc increased markedly, and that of N-ras was remarkably stimulated under the action of AAF. It appears that a cooperative action between the c-myc and N-ras oncogenes was involved in the initiation of hepatocarcinogenesis. In the promotion stage, the expression of c-myc and N-ras returned to a normal level. The expression of c-fos decreased progressively in both the initiation and promotion stages, while that of c-Ha-ras and c-Ki-ras was not much changed. The significance of these results is briefly discussed.
 ...
PMID:[Expression of cellular oncogenes during hepatocarcinogenesis in rats]. 214 11

Using an initiation--selection--promotion protocol for induction of liver tumors in Wistar rats, the modulating action of various peroxisome proliferators on neoplasia as well as on selected biochemical parameters was studied. After treatment with diethylnitrosamine (DEN), the animals were subsequently subjected to a selection procedure involving feeding of 2-acetylaminofluorene (2-AAF), and in the middle of the 2-AAF treatment, a single necrogenic dose of carbon tetrachloride. Following a recovery period, the rats were fed a diet containing 0.1% nafenopin (NAF), 0.015% perfluorooctanoic acid (PFOA), 0.05% 2,4-dichlorophenoxyacetic acid (2,4-D), 0.05% 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) or 0.05% phenobarbital (PB) as a positive control. When the animals were killed, 7 months after initiation, the incidence of hepatocellular carcinoma was 83, 33 and 16% in the animals treated with NAF, PFOA or 2,4,5-T respectively. No cancers were observed in controls, or in the 2,4,-D groups. In comparison with controls, NAF and PFOA caused a 60-and 24-fold increase inthe peroxisomal beta-oxidation of fatty acids respectively, but only about a 2-fold increase in the catalase activity, 2,4-D and/or 2,4,5-T were much less active in this respect, giving approximately a doubling in the rate of fatty acid oxidation. The specific activity of D-amino acid and glycolate oxidases were significantly depressed, whereas the urate oxidase levels were apparently unaffected by the NAF and PFOA treatment. The results suggest that the selective induction of peroxisomal fatty acid oxidation is consistent with the hypothesis that imbalance between H2O2 overproduction and its destruction could play a role in the modulation of hepatocarcinogenesis by peroxisome proliferators.
 ...
PMID:Peroxisome proliferation and modulation of rat liver carcinogenesis by 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, perfluorooctanoic acid and nafenopin. 222 20

Three protocols were used to determine the effects of dietary selenium concentration on the development of gamma-glutamyl-transpeptidase (GGT)-positive foci and hepatocellular carcinoma induced by either diethylnitrosamine (DEN) or N-acetylaminofluorene in rats. In the first experiment, foci were induced by a carcinogenic dose of DEN (100 mg/kg body weight, p.o.) at 20-22 h after two-thirds partial hepatectomy. One wk after DEN administration, during which time 0.1 ppm (representing a control level), 3.0, or 6.0 ppm selenium as Na2SeO3 was fed for 8 or 16 wk, at which time focal analysis was conducted using quantitative stereology. The results demonstrated that 3.0 and 6.0 ppm dietary selenium, initiated 1 wk following carcinogen administration, decreased focal growth rate without affecting the number of GGT foci compared to 0.1 ppm selenium. Decreased focal growth was temporary and reversible with 6.0 ppm selenium which may be related to chronic selenosis observed after 16 wk of 6.0 ppm selenium feeding. A second experiment involved a noncarcinogenic dose of DEN (25 mg/kg body weight, p.o.), then 0.1 or 6.0 ppm selenium feeding for 8 wk, followed by 0.05% phenobarbital (PB), a liver tumor promoter in a diet containing 0.1 ppm selenium. Analysis of GGT foci at 5 or 8 wk of PB feeding indicated that 6.0 ppm selenium caused a trend towards an increase in the number of foci/cm3 of liver and mean focal volume and a significant increase in GGT focal volume as a percentage of liver volume by 8 wk of PB feeding. Thus, high dietary selenium concentrations prior to PB enhance the tumor-promoting ability of PB. In a third experiment, using male Fischer 344 rats (150 g), 0.1 or 6.0 ppm selenium was fed concurrently with 0.02% AAF which was fed in a cyclic regimen. After 4 cycles, where 1 cycle equalled 4 wk of AAF, followed by 1 wk of control diet (0.1 ppm selenium), 6.0 ppm selenium significantly decreased the mean focal volume and focal volume as a percentage of liver volume, while not affecting the number of foci/cm3 of liver, again indicating a selenium effect on focal growth while not affecting the number of "preneoplastic" lesions in the liver. Six ppm selenium feeding after AAF treatment had no effect on the percentage of incidence of hepatocellular carcinoma (100%) but did cause a significant decrease in the percentage of liver volume occupied by macroscopic subcapsular liver lesions compared to 0.1 ppm selenium.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effects of dietary selenium concentration on the development of enzyme-altered liver foci and hepatocellular carcinoma induced by diethylnitrosamine or N-acetylaminofluorene in rats. 286 4

DNA methylation in eukaryotic cells is a post-replicative process involving the transfer of methyl groups from S-adenosyl-L-methionine to the 5 position of cytosine residues through the action of DNA (cytosine-5-)-methyltransferase (DNA-methylase). There are two types of methylation within the cell: a maintenance methylation and a de novo methylation. Its major function is the maintenance methylation of hemimethylated sites after replication in order to preserve the pattern from one generation to the next. Nevertheless DNA-methylase is also able to transfer methyl groups to unmethylated sites in various substrates in a de novo reaction. Male Sprague-Dawley rats have a low specific activity of liver maintenance DNA-methylase and are sensitive to the toxic and carcinogenic effects of N-hydroxy-N-acetylaminofluorene (N-OH-AAF). Female Sprague-Dawley rats, on the contrary, have a 4-5 times higher maintenance DNA-methylase activity and are 6-7 times less sensitive to this carcinogenic effect. Their de novo DNA-methylase activity is the same. When female Sprague-Dawley rats are treated with N-OH-AAF their total DNA-methylase activity diminishes. On the contrary, the maintenance DNA-methylase activity of male Sprague-Dawley rats increases, whereas the de novo activity remains constant. In the spleen, which is not a target organ, the total DNA-methylase activity decreases after injection of N-OH-AAF. These variations of DNA-methylase activity are due to a variation of extractable nuclear DNA-methylase. When Swiss mice, which are not sensitive to the carcinogenic effect, are treated with N-OH-AAF, their total DNA-methylase activity decreases. A decrease of DNA-methylase activity in response to this carcinogen seems to be correlated to the resistance of the animals in developing a hepatocarcinoma.
 ...
PMID:Variations of DNA-(cytosine-5-)-methyltransferase activities after administration of N-hydroxy-N-aminofluorene to Sprague-Dawley rats. 318 39

The dose-dependent effects of three hepatocarcinogens were investigated by measuring the number and area of glutathione S-transferase placental form (GST-P)-positive foci and nodules appearing in the liver under short-term conditions (Experiment I) and evaluating the incidence of hepatocellular carcinoma after long-term chronic administration (Experiment II). For these purposes, three different doses of 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethy-laminoazobenzene (3'-Me-DAB), and DL-ethionine (ethionine) were given to male F344 rats for 6 weeks after a single injection of diethylnitrosamine (DENA) in Experiment I or for 104 weeks without initiation by DENA in Experiment II. In Experiment I, the induction of GST-P-positive foci and nodules by 2-AAF and 3'-Me-DAB was clearly dose-dependent. In contrast, ethionine showed enhancing effects inducing GST-P-positive foci and nodules only in groups given the highest dose level. Similarly, in Experiment II, induction of hepatocellular carcinomas by 2-AAF and 3'-Me-DAB was clearly dose-dependent, whereas liver neoplasms were only induced by the highest dose level of ethionine. These results indicate that degree of induction of GST-P positive foci and nodules in a short-term in vivo test for liver carcinogens corresponds with the incidences of hepatocellular carcinomas revealed in a long-term in vivo assay.
 ...
PMID:Comparative effects of carcinogens on the induction of placental glutathione S-transferase-positive liver nodules in a short-term assay and of hepatocellular carcinomas in a long-term assay. 383 82

Studies were made on the effects of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium L-ascorbate (SA), ethoxyquin (EQ) and acetaminophen (AAF) on the induction of neoplastic lesions in the liver, kidney or urinary bladder of rats initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN), diethylnitrosamine (DEN) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The number and area of histochemical gamma-glutamyltranspeptidase-positive (gamma-GT+) foci per unit area of liver section in rats given BHA, BHT, EQ or AAP, but not SA, were significantly less than in rats given EHEN or DEN alone. Similarly, the number of hyperplastic nodules (HN) in groups given BHA or AAP and their area in groups given BHA, EQ or AAP were significantly less than in control groups. Induction of hepatocellular carcinoma (HCC) was also clearly inhibited by these three chemicals. In contrast, the incidence and quantitative values of preneoplastic lesions and renal cell adenoma in the group given EHEN were significantly increased in groups given BHA, EQ or AAP administration. For assesing the influence of BHA and BHT on urinary bladder carcinogenesis, rats received BHA or BHT after treatment with BBN. The incidences and the number per unit length of basement membrane of papilloma and carcinomas were significantly increased in rats given BHA. BHT also showed significant increase but values were less than with BHA. These results clearly demonstrated that BHA, BHT, EQ and AAP inhibit the development of gamma-GT+ foci, or HN and HCC, whereas BHA, EQ and AAP enhance the appearance of preneoplastic and neoplastic lesions in the kidney, BHA and BHT also enhancing urinary bladder carcinogenesis.
 ...
PMID:Modification of carcinogenesis by antioxidants and other compounds. 614 34

Escherichia coli DNA polymerase I (Klenow fragment), DNA polymerase alpha from both calf thymus and human lymphoma cells and DNA polymerase beta from calf thymus and Novikoff hepatoma cells can incorporate nucleotides opposite N-guanin-8-yl-acetyl-2-aminofluorene in DNA. The polymerases incorporate dCTP opposite some AAF-dG lesions when Mg2+ is the divalent cation. Substitution of Mn2+ for Mg2+ broadens the specificity of insertion: E. coli DNA polymerase I (Klenow fragment) also inserts A, and at specific sites G or T; DNA polymerase alpha inserts any of the four dNTPs with A and C incorporated preferentially to G and T. Polymerase beta is specific, inserting mainly C even in the presence of Mn2+. The Km for addition of dATP opposite a lesion by E. coli polymerase I (Klenow fragment) in the presence of Mn2+ is about 0.5 mM. dNMPs increase the insertion of nucleotides opposite AAF-dG in the presence of Mg2+ and increase both the rate and number of sites at which incorporation occurs in the presence of Mn2+. dNTP alpha S and recA protein increase only the insertion of C. We suppose that the incorporation of dCTP reflects normal base-pairing with the AAF-deoxyguanine in the anti conformation, whereas insertion of the other nucleotides (including some of the C) reflects insertion opposite the AAF adduct in its preferred syn conformation. The fact that the DNA polymerase plays a role in determining the specificity of insertion opposite a lesion terminating DNA synthesis suggests that the spectrum of base substitution mutagenesis seen in vivo may reflect the properties of the protein components, including the polymerase, involved in bypass synthesis.
 ...
PMID:A role for DNA polymerase in the specificity of nucleotide incorporation opposite N-acetyl-2-aminofluorene adducts. 649 59


1 2 3 4 Next >>