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)

Liver carcinogenesis with a single dose of aflatoxin B1 (7 mg/kg body weight) has been investigated in a group of female Wistar strain rats by repeated biopsies and necropsies. Another group received a subsequent intoxication with carbon tetrachloride by inhalation (approximately 200 doses) and another one was overloaded with riboflavin (25 parts/10(6) in drinking water). The frequency of hepatomata was almost equal in the aflatoxin and aflatoxin-carbon tetrachloride group. It was lowere in the riboflavin-aflatoxin group. In these 3 groups cirrhosis was never present in neoplastic livers. Megalocytosis was the first lesion observed. All tumoral livers had previous or concomitant megalocytosis. This modification was about as frequent, intense and widespread in aflatoxin-CCl4 and aflatoxin groups but appeared much earlier, as did the first hepatoma, in the aflatoxin-CCl4 group. It was less frequent, less intense and less widespread in the riboflavin-aflatoxin group than in the aflatoxin group. There was also a lower frequency of hepatomata in the riboflavin-aflatoxin group, but the difference was not significant due to the too small number of animals involved. The facts are not a proof of the existence of an obligatory link between megalocytosis and carcinogenesis since a slight megalocytosis was observed in the riboflavin group not affected by the neoplastic process. However, the simplest explanation of our results would be to consider that the potential tumour cells are located among the megalocytic cells, without admitting that every megalocyte is obligatorily a precancerous cell. CCl4 seems to act in shortening the time of appearance of megalocytosis. The protective effect of riboflavine should be regarded with more caution.
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PMID:Influence of carbon tetrachloride or riboflavin on liver carcinogenesis with a single dose of aflatoxin b1. 17 84

It was previously reported that the properties of alcohol dehydrogenase of a rat hepatocellular carcinoma (Becker H-252), a tumor of intermediate growth rate, were different from those of the liver enzyme, suggesting different isozymes. To determine whether the degree of differentiation affected the isozyme of alcohol dehydrogenase, a fast-growing, poorly differentiated tumor and one that is well differentiated and of intermediate growth rate were studied. Alcohol dehydrogenase from Morris hepatoma 7288ctc, a fast-growing, poorly differentiated tumor, had properties similar to those found with the Becker-H-252 tumor, including a high Km for ethanol and acetaldehyde and the absence of substrate inhibition. By contrast, alcohol dehydrogenase from the well-differentiated Morris hepatoma 5123C had properties similar to those of the liver enzyme. Thus, alcohol dehydrogenase is another example of an enzyme the isozyme composition of which changes with neoplastic de-differentiation. Further studies, including gel electrophoresis, substrate specificity patterns, and interaction with antibodies to alcohol dehydrogenase, are required to determine the factors responsible for the biochemical defect that occurs at the molecular level during carcinogenesis and whether the alcohol dehydrogenase isozymes in the Becker H-252 and Morris 7288ctc hepatomas are identical. A survey of several normal rat tissues revealed that only the stomach contains this unique isozyme of alcohol dehydrogenase.
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PMID:Kinetic properties of alcohol dehydrogenase in hepatocellular carcinoma and normal tissues of rat. 17

Orthoaminoazotoluol was administered to mice for a period of nine months. Circadian rhythms of mitotic activity and the number of the DNA-synthesizing cells were determined by autoradiography (with the use of 3H-thymidine) at the second (adenomatous nodes) and the third (primary hepatoma) stages of carcinogenesis in the developing tumours and the surrounding liver parenchyma. The listed structures proved to have a single-peak rhythm of mitotic activity with the maximum of mitoses at 4-7 a. m.; the labeled nuclei circadian rhythm was double-peaked with the maximum at 7 p. m. and 4 a. m. The mean 24-hour values of both indices at the second and third stages of hepatocarcinogenesis were much greater than in the surrounding non-tumour tissue of the liver.
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PMID:[Diurnal rhythm of cell proliferation at the late stages of precancerous changes in the liver induced by ortho-aminoazo-toluene]. 19 5

Spontaneous hepatomas and hepatic preneoplastic changes were observed in sand rats (Psammomys obesus) from two colonies. Both colonies originated from 10 sand rats captured in the Judean desert in 1969. At the age of 6 months, and increasing in multiplicity with advancing age, histologic examination revealed nodules containing hepatocytes characterized by hyperbasophilia, accumulation of glycogen, eosinophilic cytoplasm, or a mixture of these cells. In animals over 25 months old hepatocellular carcinoma was diagnosed. The histologic changes described here were reported to be characteristic of chemical hepatomagenesis in rats. No external chemical carcinogen could be demonstrated in our animal colonies, and a hereditary predisposition to tumor formation is presumed. Identity of hepatic carcinogenesis, irrespective of etiology in distantly related rodents, ie, the laboratory rat and the sand rat, which in reality is a gerbil, supports the assumption of the existence of a general law governing hepatic carcinogenesis.
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PMID:The histogenesis of hepatoma occurring spontaneously in a strain of sand rats (Psammomys obesus). 20 93

Four-week-old rainbow trout (Salmo gairdneri) were fed diets containing 0, 3, 50, 200, 400, and 800 ppm dimethylnitrosamine (DMN) for 52 weeks. At the end of 52 weeks, the fish were fed a control diet without DMN for an additional 26 weeks. Samples were taken at 26, 52, and 78 weeks to determine tumor incidence. A dose-related carcinogenic response was established from these results, and an equation was derived to relate the level of the carcinogen to the hepatocellular carcinoma incidence. From a published dose-response study that used outbred Porton rats, a second equation was derived for comparison. Rats and trout were approximately equal in their sensitivity to DMN carcinogenesis. The median lethal dose after ip injection of DMN was 1,770 mg/kg body weight in rainbow trout. Relative to the range of 15-50 mg/kg body weight reported for several mammalian species, trout were resistant to the acute toxicity of DMN.
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PMID:Carcinogenicity and acute toxicity of dimethylnitrosamine in rainbow trout (Salmo gairdneri). 20 62

Mitochondria were isolated from a slow-growing (9618A) and two intermediate-to-fast-growing (5123C, 5123tc) Morris hepatomas and host livers. The mitochondrial proteins were solubilized and fractionated on sodium dodecyl sulfate:polyacrylamide slab gels. One Coomassie blue-stained band was absent or reduced in amount in all tumors relative to host livers. In addition, a major mitochondrial enzyme present in normal liver, carbamyl phosphate synthetase, was missing or greatly reduced in the slow-growing, highly differentiated hepatoma 9618A, a tumor that is considered to be similar to normal liver in many biochemical and morphological respects. Incubation of mitochondria with [35S]methionine and a suitable amino acid incorporation system resulted in labeling of specific mitochondrial proteins. Autoradiography of the slab gels disclosed four prominently labeled fractions and a number of minor fractions. Preparations from hepatoma 5123tc demonstrated two labeled bands that were absent or greatly reduced in host liver. Host liver preparations displayed a minor band that was absent or greatly reduced in hepatoma 5123C. However, no single change in labeling pattern was common to all three tumors, suggesting the absence of a causal relationship between carcinogenesis and mutations in mitochondrial DNA.
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PMID:Differences in total mitochondrial proteins and proteins synthesized by mitochondria from rat liver and Morris hepatomas 9618A, 5123C, and 5123tc. 20 52

Examinations were made on substances that enhance or inhibit the induction of hepatoma in rats previously fed 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) for a brief period. The substances tested were stilbene, 4-nitrostilbene, 4,4'-dihydroxystilbene, diethylstilbestrol, 17beta-estradiol, and methyltestosterone. Male Donryu rats were fed 0.5 g of 3'-Me-DAB by being maintained on a diet containing 0.06% 3'-Me-DAB, and then they were fed 0.25 or 0.5 g of a test substance with the basal diet. Comparison of the development and yield of hepatomas indicated that 4-nitrostilbene and methyltestosterone had an activity of enhancing 3'-Me-DAB carcinogenesis, whereas diethylstilbestrol and 17beta-estradiol had an activity to retard it. Other substances showed no such activities. The enhancement by 4-nitrostilbene and inhibition by diethylstilbestrol of 3'-Me-DAB carcinogenesis was correlated with their effect on liver nucleic acid metabolism. Feeding of 4-nitrostilbene caused a selective inhibition of Mn2+-(NH4)2SO4-activated RNA polymerase activity of liver nuclei and reduced liver RNA content. The deleterious alteration of liver RNA metabolism was followed by the enhancement in the incorporation of ip-injected 3H-thymidine into DNA of liver nuclei. On the other hand, feeding of diethylstilbestrol increased tissue RNA content without effect on RNA polymerase activity of liver nuclei, and had an activity of increasing the incorporation of 3H-thymidine into DNA. The possible implication of these results with regard to the enhancement and inhibition of hepatocarcinogenesis is discussed.
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PMID:Enhancing and inhibitory effects of some stilbene and steroid compounds on induction of hepatoma in rats fed 3'-methyl-4-(dimethylamino)azobenzene. 20 6

The influence of synthetic estrogens on the N-nitrosomorpholine (NNM)-induced liver carcinogenesis in ovariectomized young adult female rats was investigated and compared to rats which received only the carcinogen or estrogens. Estrogens when chronically administered after the cessation of carcinogen treatment increased the carcinogenic effect of NNM. In such conditioned animals the number of nodules per number of rats was 23/31, that of hepato-cellular carcinomas 9/31, whereas in animals which received only the hepato-carcinogen the incidence of nodules and carcinomas in liver was respectively 11/31 and 3/31. Higher incidence of benign and malignant tumors in other organs was also observed in these animals. Rats which received a single dose of estrogens simultaneously with NNM developed slightly fewer tumors in liver and in other organs. Since under my experimental conditions the long-term treatment with synthetic estrogens alone did not induce any focus, nodule or hepatocellular carcinoma in the liver. I suggest that the estrogens were acting rather as tumor promotors than true initiators of liver carcinogenesis.
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PMID:The effect of estradiol-17-phenylpropionate and estradiol benzoate on N-nitrosomorpholine-induced liver carcinogenesis in ovariectomized female rats. 20 83

An hypothesis is presented which states that the endocrine systems for the synthesis of sex hormones as we know it presently might be a specialization of a system operating at the cellular level in multicellular organisms. If this were true, then a possible role of estrogens in the carcinogenesis of nontarget tissues may be postulated. Evidence for this hypothesis is highly theoretical, but is based on extrapolations from existing experimental data. The mitogenic effect of the estrogen-receptor complex is thought to be similar in both normal and malignant target tissues. Since receptors are present in several types of nontarget tissues, especially in the case of lesions at the nuclear acceptor sites, the complex might be able to cause successive mitoses in these regions, hence carcinogenesis. Several experimental approaches to test this hypothesis are presented as suggestions; these include using malignant tissues which are most likely to divide through the action of their own estrogen, such as feminizing hepatoma, and studying the mitogenic effect of locally formed estrogens through experimentation with the anti-estrogen CI-628.
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PMID:A possible role of estrogens in carcinogenesis of non-target tissues. 23 Apr 10

The possibility that carcinogens may affect methylase-mediated methylation of replicating DNA was investigated. A system eminently suitable for this purpose is liver regenerating after partial hepatectomy, as one injection of dimethylnitrosamine (DMN) given during the ensuing period of increased DNA synthesis induces hepatocellular carcinoma. Methylation of DNA by DNA methylase normally occurs only in proportion to DNA synthesis. Therefore simultaneous measurements were made of synthesis (incorporation of [14C]adenine into DNA adenine, or of d[5-3H]cytidine into DNA cytosine), and of methylation (incorporation of [methyl-3H]methionine into 5-methylcytosine of DNA) in liver regenerating after partial hepatectomy. After treatment with DMN, the ratio of methylation: synthesis remained within the normal range. Methyl methanesulphonate (MMS), a compound which damages DNA in regenerating liver in a similar but not identical way to DMN and which does not induce tumors in liver even when given after partial hepatectomy, caused an increase in methylation in relation to synthesis. These experiments therefore do not support the view that altered DNA methylase activity is involved in carcinogenesis.
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PMID:Effect of a single treatment with the alkylating carcinogens dimethylnitrosamine and methyl methanesulphonate on liver regenerating after partial hepatectomy. IV. Effect on methylase-mediated methylation of DNA. 47 54


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