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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between food intake and cancer of the large bowel was assessed by calculating the average intakes of foods, nutrients and dietary fibre in the different regions of Great Britain and relating these to the regional pattern of death from colon and rectal cancers between 1969 and 1973. No significant associations were found with the consumption of fat, animal protein or beer, nor with current estimates of total dietary fibre intake. Average intakes of the pentose fraction of total dietary fibres, and of vegetables other than potatoes, were negatively correlated with the truncated age- and sex-standardized death rates from colon cancer (r = -0.960 and -0.940). Specific components of dietary fibre may therefore inhibit colon carcinogenesis.
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PMID:Dietary fibre and regional large-bowel cancer mortality in Britain. 57 89

Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing 0.10% DL-ethionine (CDE) for 4, 6, 10, 14 or 22 weeks followed by a standard diet for up to 59 weeks. Liver sections were histochemically analyzed for the following parameters: basophilia, glycogen content and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6PASE), glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glycerin-3-phosphate dehydrogenase (G3PDH), 'malic enzyme' (MDH), alkaline phosphatase (ALKPASE) and gamma-glutamyltranspeptidase (GGT). The stop experiments revealed that many of the oval cells proliferating during the first 4-6 weeks may undergo necrotic changes and disappear with time, whereas cholangiofibroses appearing in animals fed CDE for at least 10 weeks are persistent lesions. The sequence of lesions seen in this study, leading from persistent oval cells through cholangiofibroses to cholangiofibromas, strongly suggests that the oval cells are the precursor cells of cholangiocellular tumors. The proliferating oval cells and the hepatic foci consisting of clear and acidophilic or mixed cell populations were always spatially separated and no transitions between oval and parenchymal cells were observed. These results argue against a precursor-product relationship between oval and parenchymal cells. Both proliferating and persistent oval cells, cholangiofibroses and cholangiofibromas showed a strong staining for G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT; low PHO, SYN and G6PASE activities were also detected in these lesions. Persistent glycogen-storage foci, which developed in all rats fed CDE for 4-14 weeks followed by a normal lab chow for over a year, had increased PHO, G6PDH, MDH, ALKPASE and GGT activities, while SYN, GAPDH and G3PDH activities remained unaltered and G6PASE activity decreased. Mixed cell foci appearing in animals fed CDE for 22 weeks followed by a normal lab chow for 59 weeks had strongly increased G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT activities as well as decreased G6PASE activity. These results indicate that the characteristic metabolic pattern of preneoplastic hepatic foci is independent of the further administration of the carcinogenic diet. The shift from glycogen metabolism to glycolysis and the pentose phosphate pathway occurring during the later stages of CDE-induced hepatocarcinogenesis is an autogenous process apparently directing the disturbed carbohydrate metabolism towards alternative metabolic pathways. A similar metabolic shift also seems to take place during cholangiocarcinogenesis.
Carcinogenesis 1992 Feb
PMID:Persistence of the cholangiocellular and hepatocellular lesions observed in rats fed a choline-deficient/DL-ethionine-supplemented diet. 131 Sep 7

A mixture of 100 mM creatinine and 100 mM L-phenylalanine was heated at 60 or 37 degrees C in the presence of sugar or aldehyde. A mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formed in the model system was determined by reversed-phase HPLC. Any sugars tested induced the formation of PhIP when heated at 60 degrees C, though PhIP was not detected in a mixture without sugar. Among the sugars tested, D-erythrose and D-glyceraldehyde were more productive than pentose (D-arabinose and D-ribose) and hexose (D-glucose and D-galactose) in the yield of PhIP. Moreover, PhIP was formed even when a mixture of creatinine, L-phenylalanine and D-glucose or D-ribose was incubated at 37 degrees C for a long time. Both formaldehyde and acetaldehyde also induced the formation of PhIP, though PhIP was not detected in a mixture without sugar or aldehyde even when heated at 100 degrees C. These results indicate that PhIP can be formed at low-temperature heating and that either sugar or aldehyde is essential for PhIP formation in the model system. Our data also suggest that aldehydes may be a key reactant in the formation of PhIP in aqueous heating of the mixture of creatinine and L-phenylalanine.
Carcinogenesis 1992 May
PMID:Formation of PhIP in a mixture of creatinine, phenylalanine and sugar or aldehyde by aqueous heating. 158 94

Previous studies from our laboratory have shown that dehydroepiandrosterone (DHEA), an inhibitor of glucose-6-phosphate dehydrogenase (G6PD), prevents the development of gamma-glutamyltranspeptidase (GGT)-positive foci in the early stages of hepatocarcinogenesis in rats. Since high rates of DNA and cholesterol (CH) synthesis are observed during promotion of carcinogenesis, and mevalonate (MVA), or some other intermediates of CH synthesis, could be mediators of DNA synthesis, we investigated the effect of DHEA on CH synthesis in rat liver during the development of GGT-positive foci. Hepatocarcinogenesis was induced by diethylnitrosamine in female Wistar rats by the Solt-Farber protocol (initiation/selection) with and without phenobarbital treatment. A 15 day treatment with DHEA (0.6% in the diet), started after selection, caused a great fall in labeling and mitotic indices of GGT-positive foci, which was prevented by the simultaneous administration of a mixture of four deoxyribonucleosides (DRNs) of adenine, guanine, cytosine and thymine or four ribonucleosides (RNs) of adenine, guanine, cytosine and uridine, but not by the corresponding bases. DHEA greatly inhibited G6PD activity and the production of ribulose-5-phosphate, without affecting NADPH levels, due to the compensatory increase in malic enzyme and isocitric dehydrogenase activities. Serum lecithin/cholesterol acyltransferase activity underwent a reduction in conditions allowing a rapid growth of GGT-positive tissue (absence of DHEA or presence of DHEA plus DRNs or RNs). Liver slices isolated from DHEA-treated rats showed a rise in CH content, coupled with a 80% fall in the incorporation of labeled acetate, but not of labeled MVA, into CH. A 25 day treatment of rats subjected to initiation/selection, started after the appearance of persistent nodules, caused a 36 and 78% fall in the incorporation, in vivo, of 3H2O into nodular and surrounding liver CH respectively. DRN did not counteract DHEA-induced inhibition on CH synthesis. Thus DHEA inhibits the CH biosynthetic pathway before MVA synthesis, in conditions (presence of DHEA plus DRN/RN) allowing rapid growth of preneoplastic lesions. Therefore, the development of these lesions does not need the synthesis of large amounts of CH and CH metabolites. Thus, the antipromotion effect of DHEA may depend on a decreased availability of pentose phosphates for DNA synthesis.
Carcinogenesis 1991 Sep
PMID:Differential effects of dehydroepiandrosterone and deoxyribonucleosides on DNA synthesis and de novo cholesterogenesis in hepatocarcinogenesis in rats. 168 32

Male Wistar rats were given a single i.v. injection of lead nitrate (10 mumol/100 g body wt) and were killed with matched controls 24, 48, 72 h and 20 days after the treatment. Changes of liver carbohydrate metabolism were studied histochemically testing the following parameters: glycogen content, activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6PASE), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In addition, gammaglutamyltransferase (GGT) activity was demonstrated. Between 24 and 48 h after lead nitrate injection there was a nearly complete loss of liver glycogen. Seventy-two hours later the polysaccharide reappeared in single hepatocytes and after 20 days the livers of the lead-treated animals not only had replenished their glycogen stores but contained even more glycogen than the matched controls. SYN and PHO activities were diminished from 24 to 72 h, but returned to control values after 20 days. G6PASE and GGT remained elevated up to 72 h before dropping to normal at 20 days after treatment. The pentose phosphate pathway enzymes G6PDH and 6PGDH showed the most remarkable changes in livers treated with lead nitrate. G6PDH was already elevated at 24 h, but only in Kupffer cells. At 48 and 72 h, when hepatocytes exhibited a highly increased mitotic rate, the levels of G6PDH, 6PGDH and GAPDH were elevated. After 20 days dehydrogenase activities were comparable to those of controls. The results of this study suggest that a single dose of lead nitrate not only stimulates proliferation of hepatocytes but also induces considerable changes in rat liver carbohydrate metabolism, especially between 24 and 72 h after administration. During that period glycogen metabolism undergoes a strong reduction, whereas gluconeogenesis and particularly the pentose phosphate pathway respond with a remarkable increase. This metabolic profile is most likely associated with lead biotransformation as well as with liver cell proliferation. It corresponds only partially to that found in preneoplastic and neoplastic liver lesions observed in chemical carcinogenesis, and is reversible, in contrast to the persistent alterations associated with neoplastic transformation.
Carcinogenesis 1990 Dec
PMID:Effect of lead nitrate on liver carbohydrate enzymes and glycogen content in the rat. 217 37

Following initial treatment of F344 rats with dihydroxy-di-n-propylnitrosamine, exposure to dehydroepiandrosterone (DHEA) administered in the diet at a concentration of 0.6% brought about significant decrease in weight gain, independent of food consumption, and inhibited the development of thyroid tumors and hepatocyte-altered enzyme foci. In addition to inducing a diffuse increase in glucose-6-phosphatase dehydrogenase (G6PD) and gammaglutamyl transpeptidase in the liver. DHEA treatment was associated with development of small numbers of basophilic hepatocellular foci which differed markedly in enzyme phenotype from the clear cell (glycogen storing) lesions predominating in the carcinogen-treated animals maintained on basal diet. The results are consistent with the concept that DHEA-modification of neoplastic development, as reported earlier in a number of different organs and here in the liver and thyroid, may be in some way partly mediated by changed expression of the key enzyme of the pentose phosphate pathway, G6PD, and related metabolic systems. Heterogeneity in the quality of initiated hepatocytes with regard to capacity for inhibition or promotion indicated by the present data point to the existence of more than one pathway to tumour development in the rat liver.
Carcinogenesis 1986 Feb
PMID:Modifying influence of dehydroepiandrosterone on the development of dihydroxy-di-n-propylnitrosamine-initiated lesions in the thyroid, lung and liver of F344 rats. 286 7

Dehydroepiandrosterone (DHEA) is an endogenous steroid that blocks carcinogenesis, retards aging, and exerts antiproliferative properties. In vitro, it is a potent inhibitor of glucose-6-phosphate dehydrogenase, the first committed step of the pentose phosphate pathway. In man, serum levels of DHEA and its sulfate peak in early adulthood and drop markedly with age. Epidemiologic evidence indicates that low levels of DHEA or its sulfate conjugate are linked to an increased risk of developing cancer or of death from cardiovascular disease. Like cancer, atherosclerosis is a proliferative process characterized by both initiation and promotion phases. This similarity provided a framework in which to study the antiatherogenic effects of DHEA. Rabbits were randomly assigned to four groups. Two groups of rabbits received aortic endothelial injury by balloon catheter and were fed a 2% cholesterol diet for 12 wk. DHEA, 0.5%, was incorporated into the diet of one group receiving the 2% cholesterol diet and endothelial injury and also into the diet of one of the control groups. Animals were killed after 12 wk and aortas, hearts, and livers were studied. Plasma samples were analyzed for total cholesterol, VLDL, LDL, HDL, triglycerides, DHEA, and DHEA-sulfate levels. The atherogenic insult resulted in severe atherosclerosis in animals not treated with DHEA. In those receiving DHEA there was an almost 50% reduction in plaque size (P = 0.006), inversely related to the serum level of DHEA attained. Fatty infiltration of the heart and liver were also markedly reduced. These beneficial actions were not attributable to differences in body weight gain, food intake, total plasma cholesterol or distribution of cholesterol among the VLDL, LDL, or HDL fractions. The results show that high levels of plasma DHEA inhibit the development of atherosclerosis and they provide an important experimental link to the epidemiologic studies correlating low DHEA-sulfate plasma levels with an enhanced risk of cardiovascular mortality.
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PMID:Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury. 296 22

Preneoplastic liver lesions were produced in female Wistar rats by oral administration of 2-acetylaminofluorene for 165 days succeeded by a carcinogen-free standard diet up to 420 days. During the treatment numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected histochemically by a focal decrease or lack of adenosine-5-triphosphatase and glucose-6-phosphatase (G-6-Pase) activities. In addition, the immunohistochemically demonstrable amount of L-type pyruvate kinase was clearly reduced. The histochemically demonstrated decrease of G-6-Pase was substantiated by microbiochemical determination of the enzyme activity in microdissected material. Moreover, during the experimental period a continuous decrease in glucokinase and an increase in hexokinase was detected microbiochemically within AHF and HN. These alterations indicate a shift in the carbohydrate metabolism from gluconeogenesis to glucose utilization and pentose-phosphate-pathway for biosynthesis of nucleic acids. Beside other oncofetal markers, HK may be used as indicator of the early stages of liver carcinogenesis.
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PMID:Decrease in glucokinase and glucose-6-phosphatase and increase in hexokinase in putative preneoplastic lesions of rat liver. 304 Jul 65

The endogenous synthesis of cholesterol in hepatocyte nodules, induced in male Wistar rats, by a single dose of the hepatocarcinogen diethylnitrosamine followed by a selection procedure, was investigated and was compared with that in surrounding and control tissue. In addition, the activity of enzymes related to carbohydrate metabolism (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glucose-6-phosphatase and pyruvate kinase), was measured. Hepatocyte nodules showed a striking increase in their capacity for synthesizing cholesterol, in comparison to surrounding and control tissues, and an enhancement in the activity of the pentose phosphate pathway, as indicated by increased activity of glucose-6-phosphate dehydrogenase and of 6-phosphogluconate dehydrogenase, and a concomitant decrease of glucose-6-phosphatase. The stimulation of cholesterol synthesis and of the pentose phosphate pathway was associated with increased incorporation of labelled thymidine into DNA. These data indicate that, among other metabolic disturbances, enhancement of cholesterol synthesis and of the pentose phosphate pathway, is accompanied by an increased proliferative capacity of hepatocyte nodules.
Carcinogenesis 1985 Sep
PMID:Enhancement of cholesterol synthesis and pentose phosphate pathway activity in proliferating hepatocyte nodules. 402 34

The livers from a total of 51 Sprague-Dawley rats treated with different doses of N-nitrosomorpholine (80-120 mg/l in the drinking water) for up to 14 weeks together with the livers of 28 control animals were histochemically investigated at the cessation of carcinogenic insult and at varying periods thereafter for their glycogen content, basophilia and activities of various enzymes of carbohydrate metabolism: glycogen synthetase, glycogen phosphorylase, glucose-6-phosphatase, glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase. The enzymatic patterns of normal tissue, preneoplastic and neoplastic lesions were characterized and compared with reference to the morphologically defined stages of tumor development in the liver. The early appearing glycogen storing areas, localized in the peripheral and intermediate lobular regions, did not show significant changes in the histochemically demonstrable activities of the enzymes tested. After cessation of the carcinogen treatment the more pronounced glycogen storage foci which developed within the aforementioned regions of the liver acinus usually showed a reduction in the activities of phosphorylase and glucose-6-phosphatase while the activity of glucose-6-phosphate dehydrogenase, a key enzyme for the pentose phosphate pathway, was increased. The mixed cell foci, neoplastic nodules and tumors which emerged at later stages were characterized by a progressive shift away from glycogen metabolism towards glycolysis and the pentose phosphate pathway, as indicated by an increase in glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase activities. These changes in enzyme pattern are supportive of a developmental sequence leading from glycogen storage foci through mixed cell foci and neoplastic nodules to hepatocellular carcinomas.
Carcinogenesis 1982
PMID:Correlative histochemistry of some enzymes of carbohydrate metabolism in preneoplastic and neoplastic lesions in the rat liver. 629 53


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