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 effect of enhanced cell replication induced by partial hepatectomy (PH) in aflatoxin B1 (AFB1)-induced hepatocarcinogenesis has been studied in rats of the inbred As2 strain. Animals were given 0.25 mg/kg body weight of AFB1 as a single intraperitoneal dose 24 h after PH. Non-hepatectomized animals given the same dose of AFB1 served as controls. Neoplastic nodules and hepatocellular carcinoma (HCC) were detected respectively in 100% and 90% of hepatectomized animals sacrificed between 55 and 65 weeks after AFB1 administration. None of the ten non-hepatectomized rats sacrificed at this time interval showed HCC or neoplastic nodules. On histochemical staining the tumour population was found to be heterogeneous. Thus PH resulted in enhancement of AFB1-induced hepatocarcinogenesis in rats of the AS2 strain.
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PMID:Enhancement of aflatoxin B1-induced hepatocarcinogenesis in rats by partial hepatectomy. 246 51

The effect of Rhizopus delemar on the carcinogenicity in rats of Aflatoxin B1 was studied. The Aflatoxin B1 was administered in free drinks to each male wistar rat at 126 micrograms per week such that a total dose of 3.40 mg was given over a period of 27 weeks. The culture abstract of Rhizopus delemar was added simultaneously to a group of these rats by mixing the Aflatoxin B1 solution. Animals were killed separately during 18th, 30th, 38th and 52nd week. Liver cell altered foci and neoplasms were qualified by using light microscopic and electromicroscopic morphology, by the morphometry and by the enzymic reactions. In the group of Aflatoxin B1 the incidence of hepatocellular carcinoma was 71%. In the group receiving Rhizopus delemar together with Aflatoxin B1, the hyperplastic foci and pathological enzymic foci were decreased at all times pointed and atd at termination, and in none of the rats had liver neoplasms appeared. The result of this experiment showed that the Rhizopus delemar has intensive capacity in inhibiting the toxic damage and carcinogenicity of the liver by the Aflatoxin B1, because it is not only able to postpone the appearance of altered foci and to control their development but also to accelerate their withdraw in advance. The Rhizopus delemar can be used as a feasible and efficacious means to control the intoxication of Aflatoxin B1.
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PMID:A study on the inhibition of aflatoxin B1 induced hepatocarcinogenesis by the Rhizopus delemar. 251 99

We examined the roles of the hepatitis B virus and aflatoxin B1 in the development of primary hepatocellular carcinoma (PHC) in a cohort of 7917 men aged 25 to 64 yr old in southern Guangxi, China, where the incidence of PHC is among the highest in the world. After accumulating 30,188 man-yr of observation, 149 deaths were observed, 76 (51%) of which were due to PHC. Ninety-one% (69 of 76) of PHC deaths were hepatitis B surface antigen (HBsAg) positive at enrollment into the study in contrast to 23% of all members of the cohort (RR = 38.6). Three of the four patients who died of liver cirrhosis also were HBsAg positive at enrollment. There was no association between HBsAg positivity state and other causes of death. Within the cohort, there was a 3.5-fold difference in PHC mortality by place of residence. When estimated aflatoxin B1 levels in the subpopulations were plotted against the corresponding mortality rates of PHC, a positive and almost perfectly linear relationship was observed. On the other hand, no significant association was observed when the prevalence of HBsAg positivity in the subpopulations was compared with their corresponding rates of PHC mortality.
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PMID:Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China. 253 5

Several compounds were evaluated in nonhuman primates for their potential to induce neoplasms, especially hepatocellular carcinoma (HCC). The compounds can be classified into three groups: food contaminants, model rodent carcinogens, and nitrosamines. All three compounds in the food contaminants group, namely, aflatoxin B1, sterigmatocystin, and methylazoxymethanol acetate, induced HCC. None of the model rodent carcinogens tested consistently induced HCC in rhesus and cynomolgus monkeys. Three of four nitrosamines evaluated induced HCC in rhesus and cynomolgus monkeys. One nitrosamine, diethylnitrosamine, is a predictable and potent inducer of HCC and is useful for establishment of a nonhuman primate model for numerous oncologic studies.
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PMID:Induction of hepatocellular carcinoma in nonhuman primates by chemical carcinogens. 255 97

The influence of hypothyroidism on AFB1 carcinogenesis in inbred Wistar rats was studied. The primary AFB1 hepatocarcinogenesis was significantly delayed and reduced. The transplantable hepatomas showed prolonged latency periods in rats of both sexes, and in males decreased tumor weights and a lower number of lung metastases were observed. The level of GGTP in serum and liver paralleled the advancement of morphological hepatic lesions, and the activity of serum GGTP in hypothyroid bearers of the transplantable hepatoma was lower in females than in males. It was concluded that the lack of thyroid hormones during the latency period of primary and transplantable hepatomas is decisive for delayed AFB1 carcinogenesis.
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PMID:Primary and transplantable hepatomas induced by aflatoxin B1 in hypothyroid rats. 256 20

An immunohistochemical technique was used to localize the major constitutive cytochrome P450 isozyme, P450 LM2, and the major beta-naphthoflavone-inducible isozyme, P450 LM4b, in the livers of untreated and aflatoxin B1 (AFB1)-initiated, tumor-bearing rainbow trout. In hepatic tissue sections from untreated trout, no regular anatomical pattern within the hepatic parenchymal cells could be discerned for either isozyme. Immunostaining was observed for P450 LM2 along the sinusoidal border of some of the parenchymal cells, there was moderate staining within the cytoplasm of most cells, and there were focal areas of increased staining. There was intense, uniform immunostaining for P450 LM2 within the cytoplasm of the bile duct cells, in the endothelial lining of arterioles, and along the epithelial surface of the gall bladder. Staining for P450 LM4b in livers from untreated trout was barely detectable. In liver tissue sections from AFB1-treated tumor-bearing fish, P450 LM2 appeared to be reduced and P450 LM4b was absent in the hepatocellular carcinoma nodules. An apparent increase in immunostaining for P450 LM4b was observed in nonneoplastic cells juxtaposed next to neoplastic cells as well as in areas distant to the tumors. These results may indicate that the pattern of P450 isozymes is altered in nonneoplastic cells of tumor-bearing trout livers.
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PMID:Cytochrome P450 isozyme distribution in normal and tumor-bearing hepatic tissue from rainbow trout (Salmo gairdneri). 265 90

The expression of c-myc protein was studied in primary cultures of rat hepatocytes and rat liver-derived epithelial cell lines. The levels of the protein were determined by flow cytometry using a monoclonal antibody to the c-myc protein. Freshly isolated hepatocytes from normal adult male Fischer F344 rats had low but detectable levels of the protein which were similar in the different ploidies. Higher levels were detected in immortalised but untransformed rat liver cell lines, and increased expression was observed during passage through the cell cycle. Following in vitro transformation of one of the immortalised epithelial cell lines by ras genes, similar levels of c-myc expression to those present in the untransformed cells was maintained. Transformation by activated aflatoxin B1 (AFB1) resulted in lower levels of expression. The cell cycle related level of expression was also seen in the transformed cells. Similar results to those observed in the in vitro ras transfected liver-derived cell lines were obtained from in vivo AFB1-induced rat hepatoma cell lines. These results demonstrate that continuously dividing rat liver-derived cell lines have higher levels of expression of c-myc protein than non-dividing, freshly isolated hepatocytes, and that there is no further elevation in the levels observed when these cell lines are transformed. In some cases decreased levels can result from malignant transformation.
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PMID:The expression of c-myc related to the proliferation and transformation of rat liver-derived epithelial cells. 266 Aug 95

The metabolism of chemical carcinogens was investigated in liver preparations from 28 captive woodchucks (Marmota monax). Of these, 23 were naturally infected with the woodchuck hepatitis virus (WHV), and eight also had primary hepatocellular carcinoma (PHC). Twenty-nine parameters were investigated in liver subcellular fractions, including cross-reactivity with HBsAg, and biochemical parameters, such as gamma-glutamyl transpeptidase, cytochrome P-450 and microsomal monooxygenases (aryl hydrocarbon hydroxylase, ethoxycoumarin and ethoxyresorufin deethylases, aminopyrine and dimethylnitrosamine demethylases, and testosterone 7 alpha-, 16 alpha- and 6 beta-hydroxylases), uridine 5'-diphosphoglucuronosyl transferase, GSH and related enzymes (peroxidase, reductase and S-transferase), as well as other cytosolic enzyme activities (glucose 6-phosphate and 6-phosphogluconate dehydrogenases, NADPH- and NADH-dependent diaphorases, and DT diaphorase). In addition, liver preparations were used in order to quantify the metabolic activation into bacterial mutagens of five procarcinogens (aflatoxin B1, the pyrolysis products Trp-P-2 and MeIQ, 2-aminofluorene and dimethylnitrosamine) and the decrease of potency of three direct-acting mutagens (sodium dichromate, ICR 191 and 4-nitroquinoline 1-oxide). WHV infection produced a significant stimulation of carcinogen metabolism, as shown by the simultaneous change in detoxification parameters (GSH depletion) and activation indices (enhancement of microsomal monooxygenases and of procarcinogen activation into mutagenic metabolites). There were no significant differences between WHV-positive samples from animals without PHC and the noncancerous tissue of PHC-bearing animals, whereas a decrease of both activation and detoxification indices was recorded in the tumorous tissue. There was a considerable interindividual variability among WHV carriers, which was tentatively ascribed to genetic factors. Pregnancy was the only known factor influencing the results in WHV carriers. However, even by excluding pregnant animals, the effects on carcinogen metabolism produced by WHV infection were still statistically significant. These results, together with previous data obtained in humans, revealed that metabolic factors may play a role in the synergism between viral hepatitis and chemical hepatocarcinogens in the etiopathogenesis of PHC.
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PMID:Enhanced metabolic activation of chemical hepatocarcinogens in woodchucks infected with hepatitis B virus. 272 Sep 3

The growth modulatory effects of a rat liver-derived growth inhibitor (LDGI), transforming growth factor beta 1 (TGF-beta 1), and recombinant tumor necrosis factor (rTNF-alpha) were examined in a variety of liver-derived and nonliver-derived normal and neoplastic cell culture systems. Normal rat liver epithelial (RLE) cells were highly sensitive to the growth inhibitory effects of LDGI (ID50 = 0.2 ng/ml) and TGF-beta 1 (ID50 = 0.25 ng/ml) but were less sensitive to rTNF-alpha (ID40 = 5000 Units/ml). Aflatoxin B1-transformed RLE cells showed sensitivity to the cytostatic effects of LDGI (ID50 = 1.5 ng/ml); however, these cells were completely resistant to the antiproliferative effects of TGF-beta 1 and rTNF-alpha. Clones isolated from these transformed cells, exhibited a wide range of sensitivities to LDGI but all of the clones were resistant to the growth inhibitory effects of both TGF-beta 1 and rTNF-alpha. Rat hepatoma Reuber cells were extremely sensitive to the antiproliferative effects of rTNF-alpha (ID50 = 10 Units/ml) but exhibited sensitivity to LDGI only at concentrations above 1.5 ng/ml and were resistant to the antiproliferative effects of TGF-beta 1. Rat hepatoma UVM 7777 cells and human hepatoma HepG2 cells, however, were insensitive to the growth inhibitory effects of all three factors. Among the nonliver-derived cells, human breast carcinoma (MCF-7) cells were extremely sensitive to rTNF-alpha (ID50 = 20 Units/ml, exhibited some sensitivity to LDGI (ID50 = 1 ng/ml), and were resistant to the antiproliferative effects of TGF-beta 1. In contrast, the rate of DNA synthesis is rat kidney fibroblasts and human foreskin fibroblasts was significantly stimulated in response to TGF-beta 1, LDGI, and rTNF-alpha. These data demonstrate that LDGI, TGF-beta 1, and rTNF-alpha exert positive and negative modulations of growth in different cell systems and that the growth regulatory effects of LDGI differ from those of TGF-beta 1 and rTNF-alpha in some cell types.
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PMID:Growth modulatory effects of a liver-derived growth inhibitor, transforming growth factor beta 1, and recombinant tumor necrosis factor alpha, in normal and neoplastic cells. 280 9

Genetic toxicology assays that rely on S9 microsomal mixes are subject to artifacts related to the generation of mutagenic metabolites by acidic pHs, variation in individual isolations of microsomes and the failure of subcellular fractions to faithfully produce metabolites generated in intact cells. We have developed a gene mutation assay utilizing the human hepatoma cell line HepG2, which has been shown to metabolize a broad spectrum of promutagens. Optimal conditions for assaying the induction of 6-thioguanine-resistant mutants in this cell line include: 1) growth of colonies for three weeks on lethally irradiated feeder layers of 10(6) thioguanine-resistant HepG2 cells (average plating efficiency = 60-80%); 2) a thioguanine concentration in selection dishes of 10(-4) M with a maximum seeding density of 2.5 x 10(5) cells per 100 mm culture dish; and 3) a minimum expression time of 6 days. In addition to ultraviolet light C (254 nm), a cytochrome P450 (cyclophosphamide)-dependent and a cytochrome P448 (aflatoxin B1)-dependent promutagen were shown to induce cytotoxicity and mutations in this test system. The present studies, therefore, suggest that the HepG2 cell line may be useful for a variety of assays in genetic toxicology.
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PMID:Use of an established human hepatoma cell line with endogenous bioactivation for gene mutation studies. 285 51


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