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)

Changes in the levels of serine dehydratase and glucose-6-phosphatase induced by dietary stimuli or starvation in hyperplastic nodules of rat liver during diethylnitrosamine or N-2-fluorenylacetamide feeding were studied by immuno- and enzyme histochemical methods. The study was performed during carcinogenesis through a combined method of enzyme histochemistry and radioautography. Serine dehydratase was observed diffusely in the cytoplasm of the original hepatocytes in the periportal zone and was induced markedly during diethynitrosamine feeding but only slightly during N-2-fluorenylacetamide feeding. The enzyme was deficient and not inducible in hyperplastic nodules during their developing phase. Later during the feeding period, however, there was an elevation of the level of serine dehydratase and its inducibility with time in the majority of the nodules. A good correlation was observed between serine dehydratase and glucose-6-phosphatase in their elevated levels and response to enviornmental stimuli. There was a minor group of hyperplastic nodules in which the deficiencies of these enzymes persisted and enzyme induction was not observed. A greater number of hyperplastic nodules with persistent enzyme deficiency was seen during diethylnitrosamine carcinogenesis. These results provide further information about the changing biological nature of hyperplastic nodules with respect to their metabolic adaptability and enzyme levels during hepatocarcinogenesis.
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PMID:The regulation of serine dehydratase and glucose-6-phosphatase in hyperplastic nodules of rat liver during diethylnitrosamine and N-2-fluorenylacetamide feeding. 16 97

The relationship of the rate of extraction of circulating glutathione (GSH) to the level of activity of gamma-glutamyltransferase (GGT) of hepatocytes of nodular and of cancer-bearing livers was studied in rats perfused in situ via the portal vein. Fischer adult male rats with many nodules (10 rats) or few (nine rats) liver nodules and four rats with hepatomas were compared as to their ability to remove GSH (10 microM) from the perfusate. The rate of extraction of infused GSH was directly proportional to the numbers of GGT(+)-hepatocytes in the liver tissue, inhibitable completely by adding the GGT inhibitor serine borate at 6-8 mM in the perfusate, and significantly enhanced in all rats by adding the gamma-glutamyl acceptor glycyl-glycine to the perfusate. These results suggest that nodules and cancers are able to remove GSH much more efficiently from the circulation than the surrounding liver tissue and that their enhanced GSH utilization is directly dependent on their GGT activity, which is present at much higher levels than in the surrounding tissues. The increases in GGT activity in nodule hepatocytes and enhanced ability to utilize GSH could be critical factors in the response to resistance selection of chemical hepatocarcinogenesis.
Carcinogenesis 1991 Dec
PMID:Utilization of circulating glutathione by nodular and cancerous intact rat liver. 168 39

The effects of the renal tumor promoters; beta-cyclodextrin (beta-C), DL-serine (DL-S), basic lead acetate (LA), trisodium nitrilotriacetate monohydrate (NTA) and potassium bromate (KB), and diethylene glycol (DEG) as a negative control, on early stage of renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N-hydroxyethylnitrosamine (EHEN) administration. Wistar male rats were fed 1000 ppm EHEN diet for 2 weeks and the left kidney was removed at week 3, then the animals were divided into 7 groups of 15 rats each. These groups received the following treatments: 1000 ppm LA, 10000 ppm NTA or 500 ppm KB diet for 18 weeks from week 3; 45 mg/100 g body wt./day of beta-C injected sc for 7 days; 100 mg/100 g body wt. of DL-S injected sc biweekly for 6 weeks; 5% DEG in drinking water as a negative control for two days. Five rats in each group were killed at weeks 8, 12 and 20 and their kidneys were examined histologically. At week 20, the average numbers of adenomatous hyperplasias seen as preneoplastic lesions in the beta-C, DL-S, LA, NTA or KB groups were significantly higher than those in the DEG or control groups. Thus within a relatively short period of 20 weeks, promoting effects of chemicals can be detected as a significant increase of adenomatous hyperplasias in this model.
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PMID:Possible application to medium-term organ bioassays for renal carcinogenesis modifiers in rats treated with N-ethyl-N-hydroxyethylnitrosamine and unilateral nephrectomy. 177 62

Okadaic acid is both a potent inhibitor of protein serine/threonine phosphatases and a tumor promoter in the mouse skin model. We have previously shown that at non-toxic nanomolar concentrations okadaic acid reversibly inhibits induction (promotion) by PDGF of transformed cells by the 'complete' and 'two-stage' protocols in the C3H/10T1/2 mouse fibroblast transformation assay. In the present study we have demonstrated that treatment of confluent and proliferatively quiescent C3H/10T1/2 mouse fibroblasts with low doses of okadaic acid inhibits the platelet-derived growth factor (PDGF)-induced mitogenic response. This inhibition is accompanied by a loss of PDGF binding sites, a decreased PDGF-induced phosphatidylinositol turnover and a decrease in the PDGF-induced intracellular calcium signal. The decrease in the PDGF-generated intracellular signalling processes represents a mechanism by which okadaic acid inhibits PDGF-induced proliferation and the promotion of in vitro neoplastic transformation by PDGF.
Carcinogenesis 1991 Apr
PMID:Okadaic acid inhibits PDGF-induced proliferation and decreases PDGF receptor number in C3H/10T1/2 mouse fibroblasts. 184 70

Endothelial cells produce and secrete a large number of proteases which are implicated in various disease states. These proteases fall into two classes: serine proteases include plasminogen activators (t-PA) and urokinase (u-PA) and play a major role in fibrinolysis, tissue repair and carcinogenesis; and metalloproteases include collagenases and stromelysine, two enzymes involved in the tissue remodelling that occurs during angiogenesis and tumor growth. The authors have recently identified two other proteases in porcine aortic endothelial cell culture medium. One is an elastase-like enzyme of the metalloprotease group, whereas the other is a new protease whose molecular weight is 85 Kd and whose activity becomes apparent only after exposure of the endothelial cells to platelets. The term Platelet Endothelial Cell Activated Protease accurately describes this enzyme. PECAP degrades casein and fibrinogen. Because PECAP is not inhibited by the usual inhibitors of the various classes of proteases, it remains at present unclassified.
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PMID:[Endothelial cell proteases and their modulation by platelets]. 229 Jun 90

Creatine or one of 15 amino acids were mixed with minced pork before broiling at 200 degrees C. Total mutagenic activity and reversed-phase HPLC-separated mutagenicity profiles were determined for the crust and pan residue of all samples and also in the aerosol fraction of the smoke formed during cooking of the creatine-fortified samples. Addition of 5% (w/w) creatine increased the total mutagenicity 4-fold without changing the mutagenicity profile of either crust, pan residue or aerosol. Amino acid addition (1% w/w) increased the total mutagenicity between 1.5 (lysine) and 43 times (threonine). In most cases the mutagenicity profiles of crust and pan residues were changed by amino acid addition. Dry-heated mixtures of amino acids and creatine were all mutagenic with a 250-fold range between the amino acids. The production of known food mutagens in these mixtures was analyzed by LC-MS of HPLC-fractionated mutagenic peaks. Serine, threonine, phenylalanine, alanine, leucine and tyrosine were all shown to give rise to one of the known food mutagens 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-trimethylimidazopyridine (TMIP). Lyophilized and subsequently fried meat patties and a heated powder of lyophilized meat juice were both mutagenic, with mutagenicity profiles similar to the regular meat crust, showing that water is not a prerequisite for mutagen formation in meat. MeIQx, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-di-MeIQx) and PhIP were shown, by LC-MS, to be present in the dry-heated meat juice. It is concluded that creatine and free amino acids are the main reactants of the mutagen-forming reactions that occur during frying of meat. Creatine is probably a necessary part of all of these reactions; what specific compounds are formed in each case therefore depends upon the levels in the meat of certain free amino acids and their interactions with other, as yet unknown, compounds in the meat.
Carcinogenesis 1989 Dec
PMID:Influence of creatine, amino acids and water on the formation of the mutagenic heterocyclic amines found in cooked meat. 259 Oct 18

Effects of sex steroids on pancreatic carcinogenesis during the early stage were studied in azaserine-treated rats of both sexes. Fischer rats were given weekly i.p. injections of azaserine (30 mg/kg) [CAS:115-02; diazoacetate serine(ester)] at 2 and 3 weeks of age and were divided into six groups. Castration, ovariectomy, and s.c. implantations of either a 0.3-mg or a 1.0-mg 17 beta-estradiol (CAS:50-28.2; estradiol) pellet were performed at 7 weeks of age. The groups were as follows: group 1, intact male; group 2, castrated; group 3, castrated plus 0.3 mg estradiol; group 4, castrated plus 1.0 mg estradiol; group 5, ovariectomized; and group 6, intact female. Rats were killed 4 months after the last injection of azaserine. Azaserine treatment induced atypical acinar cell foci and nodules (AACN) in both sexes. The acidophilic AACN are considered preneoplastic lesions. An apparent sex difference was observed; the number of acidophilic AACN was greater in male rats than in female rats. Castration caused a significant decrease in both the serum testosterone levels and the number of acidophilic AACN, which were comparable to those in ovariectomized female rats. Furthermore, when estradiol treatment was administered to the castrated male rats, a linear decrease in the number of acidophilic AACN and an elevation in the serum estradiol levels were observed and were dose dependent. There were also positive relationships between estradiol treatments and the mean pituitary and pancreas weights. These results showed that estradiol treatment and the drop in testosterone levels caused by castration were highly effective in inhibiting the development and growth of preneoplastic lesions of the pancreas of the rats treated with azaserine. This estradiol effect was dose dependent. The present study, therefore, provides evidence that estrogen may act as an inhibitor and androgen as a promoter in the early stage of pancreatic carcinogenesis in rats.
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PMID:Inhibitory effects of estrogen and castration on the early stage of pancreatic carcinogenesis in Fischer rats treated with azaserine. 270 21

Methionine and serine in combination enhanced the inhibitory effect of selenite on cell growth and DNA synthesis of the MOD mammary epithelial cell line. These amino acids also increased the levels of a 58-kd selenoprotein which has been correlated with selenite's effects in previous studies. The use of the amino acids accelerated the onset of inhibition of DNA synthesis by selenite and increased the rate of actual selenoprotein synthesis. The mechanism of enhancement of selenite's effects was possibly due to the amino acids increasing the levels of essential precursors (i.e. seryltRNA(UGA), HSe-) needed for selenoprotein synthesis.
Carcinogenesis 1988 Oct
PMID:Serine and methionine enhancement of selenite inhibition of DNA synthesis in a mouse mammary epithelial cell line. 313 18

The induction of a novel Ca2+-dependent protease in rat liver treated with various liver promoters, as well as its increase in preneoplastic lesions during liver carcinogenesis, was demonstrated. Six groups of male Fischer 344 rats (150 g body weight) were fed separately diets containing one of the following promoters: 0.05% phenobarbital (PB), 0.05% dichlorodiphenyltrichloroethane (DDT), 0.25% ethyl-alpha-chlorophenoxyisobutyrate (CPIB), 0.5% butylated hydroxytoluene (BHT), 10 ppm 17-alpha-ethynylestradiol (EE), and 0.05% of the non-promoter diphenylhydantoin (DH). After feeding the indicated diets for 1 week, rats were killed and protease activity in the microsomal fraction of liver tissue was determined using N-benzoyl-L-tyrosine ethyl ester as substrate. The activity of protease increased 3- to 5-fold after treatment with the promoters and compared with normal liver; the non-promoter (DH) induced a slight increase in activity. Hyperplastic nodules were induced according to the method of Solt and Farber. The activity of protease was significantly high in these preneoplastic lesions compared with the surrounding liver tissue. Biochemical characterization of this protease revealed the following properties: high Ca2+ dependency, different molecular weight and optimum pH from previously reported proteases, and preferential distribution in the SER fraction. These results suggest that a novel type of protease is induced specifically in the liver by promoters of liver carcinogenesis. The possible importance of this protease in the carcinogenic process is discussed.
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PMID:Induction of a novel Ca2+-dependent serine protease in rat liver treated with various promoters of liver carcinogenesis. 355 69

The effects of amino acids on the enhanced agglutinability of bladder cells with concanavalin A induced by subcarcinogenic treatment with N-butyl-N-(4-hydroxybutyl)nitrosamine were examined. The amino acids examined were L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-cysteine, L-glutamic acid, L-glutamine, L-glycine, DL- and L-histidine, L-hydroxyproline, L-isoleucine, D- and L-leucine, L-lysine, L-methionine, DL- and L-phenylalanine, L-proline, L-serine, L-threonine, DL-, D- and L-tryptophan, L-tyrosine and D- and L-valine. They were added to powdered diet at a concentration of 2.0%. L-Leucine, L-isoleucine, L-valine, DL- and D-tryptophan prolonged the period during which the bladder cells showed enhanced agglutinability with concanavalin A. Leupeptin, a protease inhibitor, and L-leucyl-L-leucine were also examined at a concentration of 0.1% because of their similar chemical structures, and were found to have the same effect. The tumor-promoting effects of DL-tryptophan and leupeptin have already been established by in vivo carcinogenesis experiments. The effects of L-leucine, L-isoleucine, L-valine, D-tryptophan and L-leucyl-L-leucine, detected by this short term assay, suggest that these compounds may also be promoters of bladder cancer in rats.
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PMID:Detection of amino acids as possible promoters of bladder cancer in rats by measuring their enhancement of agglutination of bladder cells by concanavalin A. 716 May 80


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