Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the alpha-fetoprotein (AFP) gene methylation of DNA from livers of rats fed choline-devoid or control choline-supplemented diets, and from hepatocellular carcinomas induced by the choline-devoid diet. Chronic choline deficiency caused a reduction in the level but not the pattern of methylation in hepatocytes. The tumors, however, had an altered methylation pattern with a marked increase in methylation at the 3' end, even those tumors that had low average DNA methylation. At the same time, there was a decrease in DNA methylation at the 5' end. The tumor methylation pattern resembled that of the active AFP gene of fetal liver but there was no increase in the steady-state level of AFP mRNA in the tumors. The 3' demethylated region is characteristic of the inactive adult liver AFP gene, but it disappears in the final stages of neoplastic transformation of hepatocytes. The methylation changes are not sufficient to activate the gene.
Carcinogenesis 1987 Feb
PMID:alpha-Fetoprotein gene methylation and hepatocarcinogenesis in rats fed a choline-devoid diet. 243 69

Albumin and alpha-fetoprotein (AFP) are two plasma proteins synthesized by the liver and the yolk sac. The production of these major proteins is subject to considerable and characteristic variations during both the course of development and hepatic carcinogenesis. It is therefore a system of choice for the analysis of genetic expression during normal differentiation and the cancerous state of eukaryotic cells. The knowledge of regulatory mechanisms at the cellular and molecular levels of the albumin and AFP genes has recently made great progress: 1) the cells which are responsible for the synthesis of albumin and AFP in the liver and other organs have been defined by conjointly using in vitro and in vivo molecular hybridization techniques; 2) the organization of these genes and their adjoining regions has been established in the rat, the mouse and man; 3) the level at which the synthesis of these two proteins is regulated has been determined; it is the transcriptional level. The transcriptional regulation of the albumin and AFP genes could be the result of genome and/or chromatin conformation level modifications. Different groups have shown that: 1) the global structure of the albumin and AFP genes does not change during the course of development and hepatic carcinogenesis; 2) modifications at the level of the methylation of certain specific cytosines could be associated with the variations in the transcription of these genes; 3) global or local (hypersensitive sites with DNase I) changes of chromatin conformation could be correlated to the potential or the overt activity of the transcription of these genes. Very recently certain 'regulatory' regions having cis 'enhancer' or 'silencer' properties have been detected upstream from the albumin and AFP genes. These regions are hypothesized to be DNA 'target' sequences on which trans-acting regulatory factors are fixed and which control the transcription of these genes. Starting from the framework of this recent work, a model of albumin and AFP gene regulation is proposed.
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PMID:The regulation of albumin and alpha-fetoprotein gene expression in mammals. 244 87

Fetal rat liver cells derived from 19-day gestation rats were exposed in culture to the carcinogen, 3'-methyl-4-dimethyl-aminoazobenzene (MDAB) for 3 days and then maintained in medium supplemented with the tumor promoter, phenobarbital (PB). Tumors developed in immunodeficient mice inoculated with cells derived from cultures which had been maintained for more than 8 weeks. Histologically, three types of tumors could be distinguished. One contained epithelial-like cells, which resembled what has previously been described as 'clear' epithelial cells. The second contained cells which were more basophilic, with prominent nuclei and closely resembled the hepatoma cell line Mc-A-R-777. The third group of tumors possessed cells of both varieties. Cell lines derived from these tumors were then characterized by determining their capacity to synthesize and secrete alpha-fetoprotein, albumin and transferrin by measuring the incorporation of 35S-methionine into immunoprecipitates obtained by reaction with the respective specific antibodies and the content of the respective mRNAs were determined by hybridization to cDNAs. The activity of gamma-glutamyl-transpeptidase (GGT) and the liver specific enzyme tyrosine aminotransferase (TAT), as well as the induction of TAT by dexamethasone was also evaluated. The presence of these markers in some of the cell lines strongly suggests that they are derived from parenchymal cells. In contrast, other cell lines which morphologically resemble 'clear' epithelial cells are negative, suggesting that they may be derived from non-parenchymal epithelial cells which exist in the original culture. However, some epithelial-like cell lines derived from tumors of mixed morphology appear different to those established from tumors which contained only epithelial-like cells. These express low levels of transferrin and tyrosine aminotransferase suggesting that they may be more closely related to hepatocytes than those cells which are derived from tumors which originally comprised only epithelial cells. The absence or presence of liver markers correlates with the morphology of the respective cell lines since transferrin and TAT are only present in significant levels in those lines which comprise cells with a morphology resembling hepatoma cell lines. In cell lines which show mixed morphology, immunocytochemistry reveals that significant amounts of transferrin are only present in the parenchymal-like population. Growth rate measurements show that the faster growing cell lines generally possessed lower levels of transferrin and TAT expression. It can be concluded from these studies that it is possible to transform cells derived from fetal rat liver in culture using a hepatocarcinogen.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1989 Jun
PMID:Transformation of cultured fetal rat liver cells by MDAB and phenobarbital. Morphological, biochemical and immunocytochemical characterization of cell lines. 247 May 26

The expression of blood group-related and tumor-associated antigens was examined in pancreatic adenocarcinomas and in the normal pancreas of hamsters to determine if this expression correlated with the host blood group and/or stage of carcinogenicity, respectively. Pancreatic tumors were induced by 4 weekly treatments of hamsters with N-nitrosobis(2-oxopropyl)amine (BOP) and analyzed immunohistochemically during different stages of tumor progression with polyclonal antibodies (PoAbs) and monoclonal antibodies (MoAbs) against A, B, O and Lewis (Le) isoantigens, including X, Y and CA 19-9 monosialoganglioside (gastrointestinal cancer antigen, GICA), as well as with PoAbs detecting human carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and the beta-subunit of human chronic gonadotropin (beta-HCG). The red blood cells of both control and tumor-bearing hamsters expressed AB and Le(a+b+)-like blood group types, as detected by polyvalent antisera. However, none of the MoAbs reacted with the hamster red blood cells. In the pancreas, all PoAbs against blood group antigens reacted with hyperplastic ducts and ductules at very early stages of carcinogenesis, as well as with neoplastic lesions, but not with normal pancreatic cells, except for the acinar cells, which were stained with PoAb-B, PoAb-Lea and PoAb-Leb. None of the MoAbs showed any affinity for the normal pancreatic cells; however, they reacted to various degrees with induced hyperplastic and neoplastic tissue. Reactivities of several MoAbs with malignant cells were greater than those with hyperplastic lesions: MoAb-B was highly reactive with all induced lesions, MoAb-A less reactive, and MoAb-H and MoAb-Ley (which has 6 sugar chains) detected only some cancer cells. Neither of the two MoAb-Lex (with 5 carbohydrate chains) reacted with carcinoma cells, although they did bind to a few hyperplastic cells. Neither MoAb-Lea and MoAb CA 19-9, nor PoAbs against CEA, AFP and beta-HCG, reacted with any normal, hyperplastic or malignant cells. These results demonstrate the differential reactivity of these PoAbs and MoAbs in normal and malignant pancreatic tissue and show that blood group antigens, especially the B isoantigens, are specific markers for induced pancreatic duct tumors in hamsters.
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PMID:Blood-group antigen expression during pancreatic cancer induction in hamsters. 331 27

The effect of BCG, an immunopotentiator, on the hepatocarcinogenesis of the rat induced by 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) was investigated. After administration of 3'-Me-DAB for 6 weeks, BCG was injected to the rats at 2-week intervals for 50 weeks and the serial determinations of serum alpha-fetoprotein and morphological examination of the liver were made. In the control group, the second rise of serum alpha-fetoprotein, which reflected the occurrence of hepatoma, was seen at about 12 weeks after discontinuance of 3'-Me-DAB. On the other hand, the second rise of serum alpha-fetoprotein in the group treated with BCG was delayed about 10 weeks compared to control group, although there was no significant difference in the final incidence of hepatomas between these two groups. Infiltration of the lymphocytes was observed in the liver of rats treated with BCG without hepatoma. BCG seems to have an inhibitory effect on 3'-Me-DAB carcinogenesis of the rat, possibly by stimulating the cell-mediated immunity, although it is not strong enough to prevent the occurrence of hepatoma completely.
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PMID:Effect of BCG on hepatocarcinogenesis of the rat induced by 3'-methyl-4-(dimethylamino)azobenzene. 615 3

The cellular localization of alpha-fetoprotein (AFP) and albumin (ALB) in permissive states for AFP synthesis has been examined. The cells containing AFP associated with permissive states in the adult are similar in appearance to cells that are present during the development of fetal liver. In fetal liver, AFP is seen in most developing hepatocytes ranging from small 'oval' like cells to larger dividing hepatocytes and in cells organized in glandular structures. Following exposure to some chemical hepatocarcinogens, AFP can also be seen in small 'oval' cells, ductal-like cells, and larger atypical hepatocytes that form glandular-like structures. Following partial hepatectomy or galactosamine-induced live injury, AFP is seen in a few large parenchymal cells usually containing identifiable chromatin Cells which contain AFP almost always contain ALB as well, but for each cell type there are many more ALB containing cells than AFP containing cells. ALB and AFP containing hepatoma cells are more frequently located adjacent to tumor vessels and AFP production by hepatoma 777 in vitro is associated with the growth state of the tumor. The AFP containing cells that are seen during restitutive proliferation most likely arise from deregulation of proliferating adult hepatocytes. The non-hepatoma AFP containing cells that appear early during carcinogenesis may arise in the adult by retrodifferentiation of hepatocytes or by proliferation of stem cells. These morphologically different AFP containing cells may or may not be precursors of the hepatocellular carcinomas which develop later.
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PMID:Heterogeneity of alpha-fetoprotein(AFP) and albumin containing cells in normal and pathological permissive states for AFP production: AFP containing cells induced in adult rats recapitulate the appearance of AFP containing hepatocytes in fetal rats. 616 57

During hepatocarcinogenesis by N-2-fluorenylacetamide, the hormonal status of male Sprague-Dawley rats is modified. The testes present a reduced activity which is evidenced by a decreased spermatogenetic activity accompanied by a drastic decrease of the plasma testosterone level. In contrast, plasma progesterone and estradiol-17 beta levels were not modified despite the 80 fold augmentation of alpha-fetoprotein, an estrogen binding protein synthesized during liver carcinogenesis.
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PMID:Sex steroid hormones levels and testicular activity during hepatocarcinogenesis by N-2-fluorenylacetamide. 618 46

To investigate the variable gene activities of alpha-fetoprotein, albumin and fibrinogen polypeptides as markers of 'liver specific proteins' in different developing organs or tissues, we have used specific complementary DNA probes to detect and to quantitate alpha-fetoprotein, albumin and fibrinogen polypeptide mRNA, respectively, in RNA fractions, prepared from various tissues of rats at different stages of fetal and postnatal development and from hepatomas induced by diethylnitrosamine. The results indicate that there is no consistent relationship between sequence content of alpha-fetoprotein, albumin and fibrinogen polypeptide mRNA in different developing tissues. Intestines which are like the liver also of endodermal origin do not contain alpha-fetoprotein, albumin and fibrinogen polypeptide mRNAs, while kidneys which are mesodermal in origin were found to be alpha-fetoprotein, albumin and fibrinogen polypeptide mRNA producers in neonatal life. In yolk sac, only alpha-fetoprotein and fibrinogen polypeptide mRNA could be detected. In the liver, the increased level of albumin and fibrinogen polypeptide mRNA during fetal and neonatal development is accompanied with a diminished amount of alpha-fetoprotein mRNA. The neosynthesis of alpha-fetoprotein mRNA in the liver during carcinogenesis occurred without a decreased content of albumin and fibrinogen polypeptide mRNAs. These findings suggest that complex mechanisms of gene regulation are involved in variable gene activities of alpha-fetoprotein, albumin and fibrinogen polypeptides in cells of different organs or tissues developed from a single cell.
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PMID:Sequence content of alpha-fetoprotein, albumin and fibrinogen polypeptide mRNAs in different organs, developing tissues and in liver during carcinogenesis in rats. 618 48

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), all trans-retinoic acid (RA), 5-azacytidine (5-AC), and phenobarbital (PB) on the activities of seven enzymes and/or isozymes of a diploid rat liver epithelial cell line have been studied. At 0.1 microgram/ml, TPA depressed the specific activities of lactate dehydrogenase and gamma-glutamyl transpeptidase, whereas 2 mM PB depressed gamma-glutamyl transpeptidase and alkaline phosphatase. At 0.01 microgram/ml, RA markedly depressed the activity of NADH-diaphorase and lactate dehydrogenase but enhanced the activity of alkaline phosphatase. Only 2 microM 5-AC caused the most significant shift of lactate dehydrogenase isozyme toward the "muscle"-type isozyme. Histochemical studies revealed that PB and 5-AC induced focal areas of cells with glycogen deposits, but no significant changes in either ultrastructure or alpha-fetoprotein and albumin immunohistochemical staining pattern were observed to suggest hepatocytic differentiation. Although none of the enzymatic changes could be consistently correlated with the effects of these biological modifiers on the cellular growth rate, the effect of RA on NADH-diaphorase, lactate dehydrogenase, and alkaline phosphatase activities was the opposite of the changes observed during carcinogenesis of these rat liver epithelial cells by multiple treatments with N-methyl-N'-nitro-N-nitrosoguanidine. The depression of gamma-glutamyl transpeptidase activity by PB is contradictory to that observed histochemically in hepatocytes in vivo, but such discrepancy may be related to the differences in cell type, growth conditions, or duration of exposure.
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PMID:Biochemical effects of 12-O-tetradecanoylphorbol-13-acetate, retinoic acid, phenobarbital, and 5-azacytidine on a normal rat liver epithelial cell line. 620 84

Determination of activity of deoxycytidylate deaminase stabilized by etylene glycol was used to evaluate the rate of DNA synthesis in precancerous liver tissue and in transplantable rat hepatomas. Increased activity of the enzyme in macroscopically unchanged liver tissue occurred during hepatocarcinogenesis induced by 3'-Me-DAB in the period between weeks 1 and 10. The slow growing transplantable tumours derived from primary hepatomas induced by DAB and AF showed slightly increased activity, while the fast growing lines derived from primary tumours induced by 3'-Me-DAB were characterized by markedly increased activity. Thus the enzyme appeared to be a good marker of tumour growth rate. Correlation between increased DNA synthesis during carcinogenesis and the occurrence of alpha-fetoprotein is briefly discussed.
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PMID:Correlation of deoxycytidylate deaminase activity with cell proliferation during hepatocarcinogenesis and tumour growth in transplantable rat hepatomas. 677 98


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