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

The technique of ex-vivo isolated pancreatic perfusion has been a valuable method for investigation of the physiology of the exocrine and endocrine pancreas. We have adapted the technique of isolated pancreatic perfusion for use in the Syrian golden hamster, an animal used widely in studies of pancreatic carcinogenesis. The technique involves surgical harvest of the pancreas with its aortic and portal venous blood supply intact and perfusion of the pancreas with a modified Krebs buffer at 37 degrees C. Physiological function of the perfused pancreas system was examined in 27 Syrian hamsters. In tests of endocrine function, the perfused pancreas responded by increasing insulin secretion within 1 min of elevating perfusate glucose concentration, and also secreted insulin promptly in response to 10 mM arginine. In exocrine studies, the flow of pancreatic juice was stimulated by the addition of 0.8 X 10(-9) M secretin to the perfusate, and amylase output was significantly increased by the addition of 0.2 X 10(-9) M cholecystokinin (CCK-8). The ex-vivo isolated perfused pancreas in the hamster thus appears to respond appropriately to physiological stimuli and is a valuable additional tool for studies of the hamster pancreas.
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PMID:Ex-vivo isolated perfusion of the pancreas in the Syrian golden hamster. 369 78

Nitrosomethylisoamylamine (NMIA), a carcinogenic N-nitroso compound was synthesized from isoamylamine (IAA) in a glucose-ammonium nitrate medium after several days' incubation with fungi and subsequent nitrosation with sodium nitrate. The nitrosamine was not produced by control reactions which lacked either IAA or fungi. The yield of NMIA varied with the length of incubation after inoculation with the fungi, and with the concentrations of IAA and NaNO2, the duration of nitrosation, the pH of the medium and the species of the fungi. The optimum conditions for the formation of the nitrosamine are reported.
Carcinogenesis 1986 Feb
PMID:Synthesis of nitrosomethylisoamylamine from isoamylamine and sodium nitrite by fungi. 394 16

The binding of various chemical carcinogens to the glucose-inducible form of cytochrome (cyt.) P-450 in Saccharomyces cerevisiae was examined with reference to known metabolism in mammalian systems. All the carcinogens examined gave spectral interactions with the yeast cytochrome. The carcinogens benzo[a]pyrene and cyclophosphamide gave Type I binding, while benzidine and 2-naphthylamine gave Type II binding spectra indicating binding at the haem group. Dimethylnitrosamine gave undetectable binding in yeast microsomal fractions, but a Type I binding spectrum was seen with purified cyt. P-450 preparations. The demonstration that these carcinogens bind to yeast cyt. P-450 is discussed in the light of their genotoxicity.
Carcinogenesis 1985 Sep
PMID:Interaction between yeast cytochrome P-450 and chemical carcinogens. 402 32

Male rats were fed a selenium-deficient Torula yeast diet with or without 0.2 ppm selenium (as sodium selenite) in the drinking water. Selenium deficiency caused a significant increase of urinary acetoacetate excretion in fed rats, and 24 or 48 hours of starvation enhanced this effect. Two days of selenium supplementation decreased the amount of urinary acetoacetate and 3-hydroxybutyrate to 50% of the deficiency value, indicating an enzymatic impairment in the selenium-deficient rat. No selenium-dependent effect was found for the following: (1) urinary pH, amount of nitrite, glucose (negative), hemoglobin or protein, and the urine was negative for phenylketones; (2) blood content of glucose, acetoacetate, or 3-hydroxybutyrate; or (3) liver content of glycogen, glucose, acetoacetate, or 3-hydroxybutyrate. On the other hand, the liver content of triglycerides was significantly lower in selenium deficiency. Indications for a higher content of ketone bodies (acetoacetate plus 3-hydroxybutyrate) in the kidneys from selenium-deficient rats were found. The increased urinary excretion of ketone bodies on selenium deficiency may indicate an impairment of lipid and ketone body turnover (in the kidney), or a decreased kidney reabsorption rate. Possible implications of these results in connection with protective roles of selenium in atherosclerosis and carcinogenesis are suggested.
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PMID:Impaired ketone body metabolism in the selenium deficient rat. Possible implications. 405 13

There is growing evidence that natural killer (NK) cells play an important role in immune surveillance against tumors and certain infections. The coexistence of activated neutrophils with lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. We examined the susceptibility of lymphocyte NK activity to oxidative injury by the neutrophil myeloperoxidase (MPO) system and H2O2 with the use of a cellfree model system. Exposure of human mononuclear leukocytes (MNL) to MPO, an H2O2-generating system (glucose + glucose oxidase), and a halide (C1- or I-) resulted in marked suppression of MNL-NK activity, as measured by 51Cr release from K562 tumor targets (p less than 0.001). This suppression was dependent on the presence and activity of each system component and was blocked by azide and catalase, but not by heated catalase. In spite of the marked functional suppression of NK activity, MNL viability was more than 95% and target binding frequency was not affected. NK suppression was reversible after 24 hr in culture. The mechanism of suppression was dependent on the amount and rate of H2O2 delivered, and on MNL number. MPO was essential when H2O2 flux was low or when MNL numbers were high. As H2O2 flux increased or MNL numbers decreased, NK suppression gradually became MPO-independent and was mediated by H2O2 alone. The ability of the MPO system to compromise lymphocyte NK function may explain the in vitro inhibition of NK activity of mixed cell populations by the tumor promoter phorbol esters, because these agents are potent stimulants for neutrophil secretion of MPO and H2O2. This study may also provide a possible mechanism for the reported in situ NK activity suppression by adherent phagocytic cells during carcinogenesis in both humans and animals.
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PMID:Down-regulation of human natural killer activity against tumors by the neutrophil myeloperoxidase system and hydrogen peroxide. 609 70

A benzo[a]pyrene (B[a]P) hydroxylase activity and epoxide hydrolase (EH) activity have been found in rat liver nucleoli obtained from untreated (C) and 3-methylcholanthrene (3-MC) pretreated rats. A comparison of the enzyme activities was made in rat nuclei and nucleoli. Light and electron microscopic observations of nucleolar preparations did not reveal significant contamination either by intact nuclei or by nuclear membranes, and glucose 6-phosphatase, a marker of microsomal activity, was not detected in our nucleolar preparations. NADPH cytochrome c-reductase could be measured in C and 3-MC nuclei and very low but detectable activity was found in the nucleoli. Nucleolar preparations revealed significant hydroxylating activity, which was inducible by 3-MC in nuclei but not in nucleoli. The presence of EH in nucleoli was demonstrated with phenanthrene 9,10-oxide and B[a]P 4,5-oxide, but the nucleolar activities were lower than those obtained using intact nuclei. The addition of 1,1,1-trichloropropene 2,3-oxide completely inhibited EH activity. Furthermore the presence of covalently-bound metabolites of B[a]P formed in isolated nucleoli was demonstrated by cytofluoromicroscopy.
Carcinogenesis 1981
PMID:Presence of benzo[a]pyrene metabolizing activities in isolated rat liver nucleoli. 627 39

Aflatoxin B1, benzo[a]pyrene, N-nitrosomorpholine, procarbazine (PC) and 1,2-dimethylhydrazine (DMH) were used to investigate the efficiency of the Salmonella/rat hepatocyte assay for detecting carcinogens as mutagens. In this assay, bacteria and the test compound were co-incubated with freshly isolated rat hepatocytes and then plated onto minimal glucose agar. Factors for optimal mutagenicity, including the number of hepatocytes and the number of bacteria, the type of assay medium and the length of incubation in liquid medium were investigated. All the compounds were metabolized into bacterial mutagens. Mediation of the mutagenicity of PC and DMH by rat hepatocytes indicates that freshly isolated cells of this type are a useful alternative metabolic activation system for use in screening chemicals found to be non-mutagenic in the Salmonella/microsome assay.
Carcinogenesis 1983
PMID:Studies on the efficiency of the Salmonella/rat hepatocyte assay for the detection of carcinogens as mutagens: activation of 1,2-dimethyl-hydrazine and procarbazine into bacterial mutagens. 634 Aug 51

In an approach to testing the possible relationship between embryogenesis and carcinogenesis, we examined the susceptibility of rats carrying the grc, which is an MHC-linked gene complex affecting growth and development, to the development of the cellular and biochemical changes known to be associated with the induction of cancer. Genetically related strains which differed mainly by the presence or absence of the grc were fed a diet containing 0.02% N-2-acetylaminofluorene (AAF), and the induction of gamma-glutamyltranspeptidase (GGT)-positive foci, bile-duct proliferation and oval-cell proliferation in the livers of the two groups of animals were scored. All of the rats homozygous for the grc displayed GGT-positive foci (from three to six per section) and extensive bile-duct and oval-cell proliferation. By contrast, only 27% of the animals which did not carry the grc had GGT-positive foci in the liver, and these were present in smaller numbers (from one to three per section); there was no bile-duct or oval-cell proliferation. Biochemical studies of the liver and testes showed that the grc homozygotes had the metabolic abnormalities associated with the development of cancer: increased cholesterol biosynthesis; increased DNA synthesis, as indicated by an enhanced incorporation of 3H-thymidine into DNA; stimulation of the hexose monophosphate (HMP) pathway, as indicated by increased levels of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD); and decreased levels of circulating lipoproteins. Both the morphological response of the rats carrying the grc to feeding AAF and the biochemical abnormalities that exist in these animal are consistent with the changes which eventually lead to cancer. Thus, there appears to be a relationship in rats between aberrations in the control of growth and development, susceptibility to the chemical induction of cancer and the control of cholesterol biosynthesis.
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PMID:Enhanced susceptibility to a chemical carcinogen in rats carrying MHC-linked genes influencing development (GRC). 674 13

12-O-Tetradecanoylphorbol-13-acetate (TPA), a highly active tumor-promoting agent, rapidly accelerates deoxyglucose transport in bovine lymphocytes. This acceleration in rate is dose-dependent and proceeds without evidence of a lag period to achieve a maximal response within 10 min. Structure-activity studies showed that the activity of various phorbol derivatives for the stimulation of glucose transport closely parallels their potency as comitogens and stimulators of phosphatidyl choline synthesis in bovine lymphocytes and as tumor promoters on carcinogen-initiated mouse skin. The acceleration of glucose transport by TPA proceeds in the absence of oxygen and in the presence of retinoic acid and 5,8,11,14-eicosatetraynoic acid (ETYA). This situation is in contrast to the TPA stimulation of choline phospholipid synthesis and amino acid transport which exhibits a lag and a sensitivity to anaerobiosis, retinoic acid, and ETYA. These results suggest that the stimulation of glucose transport by TPA is an oxygen-independent early event resulting from a direct action of the tumor promoter on the cell membrane of the lymphocyte; this action of TPA appears antecedent to the oxygen-dependent/retinoid-sensitive events.
Carcinogenesis 1982
PMID:Rapid acceleration of deoxyglucose transport by phorbol esters in bovine lymphocytes. 715 Dec 54

Mixtures of creatinine, glucose and various single amino acids were heated at 180 degrees C for 10 min in an aqueous model system. The heated mixtures all showed mutagenic activity, ranging from 80 to 2400 TA98 revertant colonies/mumol creatinine with metabolic activation. Testing of HPLC fractions for mutagenic activity showed each mixture to contain several mutagenic components, some of which corresponded to known heterocyclic amines and others to unknown compounds. The presence of 2-amino-3-methyl-imidazo[4,5-f]quinoxaline, 2-amino-3,8-dimethylmidazo[4,5-f]quinoxaline and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline in most of the samples was established using HPLC with photodiode array detection and liquid chromatography/mass spectrometry with electrospray interface and single ion monitoring. In addition, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, 2-amino-1-methyl-6-phenylimidazo[4,5-f]quinoxaline, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole and the co-mutagenic compounds 9H-pyrido[3,4-b]indole and 1-methyl-9H-pyrido[3,4-b]indole were detected in some samples.
Carcinogenesis 1995 Oct
PMID:Influence of amino acids on the formation of mutagenic/carcinogenic heterocyclic amines in a model system. 758 66


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