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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Classification of rat hepatocellular proliferative lesions can vary between pathologists as the many qualitative histologic criteria have not been satisfactorily evaluated and ranked for prognostic value. Computer-assisted morphometry offers an objective method to evaluate certain cellular features. The Solt-Farber resistant hepatocyte model was used in this study to produce populations of rats with a full range of hepatocellular proliferative lesions. Cellular features within the lesions were then measured morphometrically and the data were analyzed by animal age and by subjective lesion diagnosis. The nuclear/cytoplasmic ratio followed by the cell area and nuclear area were found to be the most important parameters for separating microscopic foci and islands of cellular alteration, an early hyperplastic lesion, from other hepatocellular proliferative lesions. The coefficient of variation, as a relative measure of heterogeneity, increased in a linear manner for cell, nuclear and nucleolar areas as the animals aged and was significantly higher for cell and nuclear area in hepatocellular carcinoma compared to other hepatocellular proliferative lesions. Hepatocyte nodules (representing primarily late hyperplastic lesions) and persistent hepatocyte nodules (lesions with similarities to hepatocellular adenoma) could not be satisfactorily separated within the limits of this study. As these borderline lesions show a continuum of cytologic change, other features, such as architectural change, are necessary to satisfactorily classify them on a subjective basis. An alternative approach is to use discriminant functions derived from morphometric studies.
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PMID:Morphometric evaluation of hepatocellular proliferative lesions in the rat liver. 322 23

The effect of carcinogenesis on various hepatic microsomal parameters and related cell functions was studied in two tumor models. Hepatocarcinoma was produced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) (Solt-Farber model) and mammary adenocarcinoma using R3230 AC cancer cell line. In these models the effect of the tumor on metabolic functions of hepatocytes was studied. In the DEN/2AAF tumor model in nodules phase I components (cytochrome P-450, aminopyrine N-demethylase, arylhydrocarbon hydroxylase) were reduced, together with microsomal progesterone content and total and specific progesterone binding. Phase II components (glutathione, glutathione S-acyltransferase, UDP-glucuronyl transferase, epoxide hydrolase) were increased. In hepatoma the effects were more enhanced. Nodules grown in the speen retained the dedifferentiated enzyme characteristics. In the R3230 AC mammary adenocarcinoma phase I components of the hepatic endoplasmic reticulum were reduced, and phase II components increased. Progesterone content and receptor binding were also increased. These results indicate that enzymatic abnormalities in the liver cell are connected with cancer production and the hepatic dedifferentiation seems to be indistinguishable in tumor-bearing liver from those seen with extrahepatic neoplasms.
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PMID:Hepatic metabolism and carcinogenesis. Its role in hepatoma and adenocarcinoma. 338 80

When rats are subjected to chemical hepatocarcinogenesis according to the protocol of D. Solt and E. Farber ((1976) Nature (London) 263, 701-703), the liver exhibits elevated levels of tyrosine protein kinase activity as early as 3 weeks after the injection of diethylnitrosoamine. A more striking elevation in tyrosine protein kinase activity is noted in rat hepatomas induced by administration of chemical carcinogens, in particular that of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Tyrosine protein kinase solubilized from the particulate fraction of 3'-Me-DAB-induced hepatoma has a molecular weight identical to that of p60v-src, cross-reacts with p60v-src immunologically, phosphorylates the heavy chain of anti-p60v-src IgG, and probably belongs to a family of p60c-src. The tyrosine protein kinase from the particulate fraction of normal rat liver is indistinguishable from the hepatoma kinase in these properties; thus it apparently differs only in the level of activity. Whether the liver and hepatoma kinases differ merely quantitatively or whether they differ even qualitatively, however, remains to be elucidated.
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PMID:Tyrosine protein kinase in preneoplastic and neoplastic rat liver. 342 12

The hepatocarcinogen acetamide, in single doses of 100 and 400 mg/kg b.wt., was shown to act as an initiator in a dose-dependent fashion in rat liver using the Solt-Farber method. Acetamide and its putative metabolite N-hydroxy-acetamide did not cause liver necrosis in single dose experiments. Acetamide showed no evidence for genotoxicity in tests for mutations in Salmonella typhimurium, for DNA damage in rat hepatoma cells or for DNA repair in isolated rat hepatocytes. In contrast, N-hydroxy-acetamide displayed genotoxic activity in all 3 test systems. Neither acetamide nor N-hydroxy-acetamide induced transformation of primary Syrian hamster embryo cells or gave evidence of inhibition of metabolic cooperation in V79 cells. Radiolabelled acetamide and N-hydroxy-acetamide were not bound covalently to proteins in the presence of various metabolic activation systems (microsomes plus NADPH or xanthine/xanthine oxidase, cytosol or cytosol plus acetyl CoA or proline plus ATP). N-Hydroxy-acetamide was cytotoxic to monolayers of isolated hepatocytes at concentrations above 2.5 mM. This cytotoxicity was increased after diethyl maleate treatment, but N-hydroxy-acetamide did not deplete cellular glutathione. A HPLC system was developed for the separation and quantification of acetamide, N-hydroxy-acetamide and acetic acid. No significant excretion of N-hydroxy-acetamide or acetic acid in the urine could be demonstrated after treatment of rats with 100 or 1,000 mg/kg b.wt. of acetamide. The underlying mechanism for the observed initiating effect of acetamide is obscure.
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PMID:Studies on the mechanism of acetamide hepatocarcinogenicity. 355 Jul 69

Rat liver hyperplastic foci (HF) and hyperplastic nodules (HN) induced by diethylnitrosamine (DEN) according to the method of Solt and Farber were observed by light microscopy (LM) and scanning electron microscopy (SEM). Liver cirrhosis was not observed. HF, which were composed of basophilic hepatocytes arranged usually in two-cell-thick plates and occasionally one-cell-thick plates, were followed by early HN, which were composed of eosinophilic hepatocytes with enlarged nuclei and prominent nucleoli, at 4 weeks after DEN administration. SEM revealed that hepatocytes in HF had smooth surfaces and dilated bile canaliculi with a few short microvilli. Early HN (4 and 6 weeks) were composed of two-cell-thick plates of hepatocytes, whose intercellular surfaces were covered with numerous microvillous projections. Bile canaliculi were dilated and had numerous short microvilli. Late HN (6 and 8 months) were composed of eosinophilic hepatocytes, which were irregular in shape and size. Their nuclei were enlarged and nucleoli were prominent. Hepatocytes were arranged in two-cell-thick plates, but never in many-cell-thick plates. Bile canaliculi were larger than sinusoids. The bile canaliculi had numerous diverticula, but the zona occludens was present. Microvillous projections of intercellular surfaces of hepatocytes were more numerous than those of early HN. Fenestrae of the sinusoidal endothelium were lost in most parts. Kupffer cells were not seen in any stage of HN. HN progressed gradually toward hepatocellular carcinoma.
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PMID:Scanning electron microscopy of experimentally induced sequential alterations of rat liver hyperplastic nodules. 674 Feb 37

Rat liver hyperplastic nodules induced by diethylnitrosamine (DEN) were observed by scanning electron microscopy (SEM). Liver hyperplastic nodules were made according to the methods of Solt and Farber. Hyperplastic nodules appeared 4 weeks after DEN administration and these early hyperplastic nodules continued growing and became eosinophilic hyperplastic nodules 5 to 6 weeks after DEN administration. SEM revealed that hyperplastic nodules were composed of enlarged hepatocytes which formed two-cell-thick plates. Intercellular surfaces of hepatocytes were covered with numerous microvilli. Dilation of bile canaliculi was marked in hyperplastic nodules. Kupffer cells were not seen in the sinusoids. Sinusoidal endothelia had no fenestrae. Transmission electron microscopy revealed the endothelium had a continuous basement membrane. In conclusion, hyperplastic nodule has the intermediate features between liver cirrhotic nodule and liver cell adenoma or hepatocellular carcinoma.
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PMID:Scanning electron microscopy of rat liver hyperplastic nodules induced by diethylnitrosamine. 718 51

We studied the effect of antiandrogen treatment on the Solt-Farber model of hepatocarcinogenesis in male Sprague-Dawley rats. The size and number of the liver tumors were reduced by various antiandrogen treatments (orchiectomy, an LH-RH analog, and chlormadinone acetate). In addition, the proportion of poorly differentiated carcinomas was decreased by the antiandrogen treatment, while that of well-differentiated trabecular or glandular carcinomas was increased. The bromodeoxyuridine labeling index of the tumor cells was significantly decreased after the antiandrogen treatment. The expression of rat androgen receptor mRNA in carcinoma tissue was increased when compared to control liver tissue, and was decreased after the antiandrogen treatment. Orchiectomy had the greatest inhibitory effect on carcinoma, although the effect of chemical orchiectomy using an LH-RH analog was almost similar to that of orchiectomy. These results suggest that the clinical application of antiandrogen therapy for human hepatocellular carcinoma might be possible in the future.
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PMID:Effect of antiandrogen treatment on chemical hepatocarcinogenesis in rats. 752 37

We previously reported that LEC rats, which show a spontaneous occurrence of liver injury and hepatocellular carcinoma (HCC), are highly susceptible to chemical carcinogens such as diethylnitrosamine (DEN). Since abnormal copper accumulation in the liver of LEC rats was found to be a cause of liver injury, it is necessary to elucidate whether the carcinogen susceptibility of LEC rats is related to the accumulation of copper in the liver. In this study we have examined the relationship between the susceptibility of FI [LEC x LEA or LEC x Fischer 344 (F344)] and FI backcross rats to DEN and hepatic copper concentration, as copper accumulation has been demonstrated to be inherited as an autosomal recessive trait. The groups of F1 and F1 backcross rats were given a single intraperitoneal injection of DEN (20 mg/kg wt) and subjected to a modified Solt-Farber protocol for assaying glutathione S-transferase placental form (GST-P)-positive foci. The hepatic copper concentration was examined by atomic absorption. Although no F1 rats showed a high copper concentration in the liver, the numbers of foci were as high as those in LEC rats which accumulate copper. Backcross rats separated into high and low copper concentration groups at an almost 1:1 ratio, but there was no significant difference in the mean numbers of foci between these two groups. The results clearly indicate that the high susceptibility of LEC rats to DEN is genetically independent of copper accumulation in the liver. A possible dominant inheritance of this high carcinogen susceptibility was suggested. Biochemical measurement of cytochromes P450 and b5 in the liver of F1 rats indicated that alterations in drug metabolizing enzymes may be partially responsible for the high carcinogen susceptibility of LEC rats.
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PMID:The high hepatocarcinogen susceptibility of LEC rats is genetically independent of abnormal copper accumulation in the liver. 769 3

The aim of this study was to evaluate the effects of dietary iron on hepatocarcinogenesis in an animal model mimicking noncirrhotic genetic hemochromatosis. Iron overload may lead to liver cirrhosis and an increased risk of developing primary hepatocellular carcinoma. It is unknown if iron is of pathogenic importance for the carcinogenic process, or whether the increased cancer risk results solely from the cirrhotic process. We investigated the initiating, promoting, and mitogenic properties of carbonyl iron in the Solt-Farber model of chemical hepatocarcinogenesis. A diet supplemented with 2.5% to 3.0% carbonyl iron was either added to, or replaced, the initiating and promoting events in the model. None of the animals developed hepatic fibrosis. Hepatic iron was increased 6- to 13-fold in iron-treated animals, and predominantly located in periportal hepatocytes. Iron as an initiator did not increase the number of glutathione-S-transferase-Yp-positive foci. Iron reduced the number of foci when added to low-dose diethylnitrosamine plus partial hepatectomy, which may be explained by a delayed hepatic regeneration in iron-loaded liver. As a promoter, iron did not selectively induce proliferation of initiated cells. Added to a complete promotive regimen, iron decreased the volume density of preneoplastic nodules, possibly because of a mitostimulatory effect of iron on normal hepatocytes surrounding the nodules. Iron increased the hepatocyte labeling index and counteracted the mitoinhibitory effect of 2-acetylaminofluorene on regenerating liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of dietary iron on initiation and promotion in chemical hepatocarcinogenesis. 784 26

Structural alterations of the p53 gene were investigated in chemically induced rat hepatocellular carcinomas (HCCs), hyperplastic hepatic nodules (HPNs), and cell lines derived from rat neoplastic and normal liver cells. The mutations were detected by GC-clamped denaturing gradient gel electrophoresis using DNA that had been amplified from p53 mRNA by the reverse transcriptase-polymerase chain reaction. This method enabled us to find single-base changes within the p53 gene without using radioisotopes. The presence of mutations was subsequently confirmed by DNA sequencing. No mutations were detected in six primary HCCs and 12 HPNs induced by the Solt and Farber regimen (Nature 236: 701-703, 1976), suggesting that p53 gene mutations do not play a major role in rat hepatic carcinogenesis. However, five of seven HCC cell lines and one of two cell lines derived from normal liver cells had the mutated p53 gene and had lost the normal p53 gene. Five cell lines had a G-->T transversion at various codons, whereas one line had a 21-base deletion in exon 5. Therefore, we conclude that p53 gene mutations may occur in vitro during establishment of the cell lines or may be derived from very small populations within the primary tumors.
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PMID:Detection of p53 gene mutations in rat hepatocellular carcinoma cell lines by denaturing gradient gel electrophoresis. 835 84


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