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

Restriction of the total diet or the number of calories fed to rats and mice inhibits the formation of tumors in several tissues. Unless animals are fed equivalent levels of food, or attain equivalent body weights, it is difficult to assess the significance of the effect of other nutritional modifications on carcinogenesis. The effects of altering the levels of protein or fat are much less than those seen with dietary restriction. Feeding a protein-free diet is tolerated for a limited period and can alter the metabolism of carcinogens. It may thus affect the tumor incidence induced by one-shot carcinogens. Vitamins have specific effects on the activity of certain carcinogens, the fullest information being available for vitamin A, which has been shown to inhibit or enhance carcinogenesis, and vitamin C, which by reducing sodium nitrite, prevents nitrosation of secondary and tertiary amines occurring in acidic conditions of the stomach. Inorganic substances, such as iodine (thyroid) and copper (liver), may affect the tumor incidence in specific tissues. The metabolic activation of carcinogens is modified by enzyme induction and the administration of antioxidants. The relevance of these results to the induction of cancer in humans is briefly discussed.
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PMID:Nutrition and experimental carcinogenesis: a review. 5 97

Purified native Hemophilus influenzae DNA is relatively insusceptible to nitrous acid (NA) mutagenesis in vitro, but is readily mutated following denaturation. NA mutagenicity for duplex DNA is significantly increased in the presence of various alcohols, glycols, phenols or primary amines. Phenol-extracted DNA contains dissociable contaminants of low molecular weight that enhance NA mutagenesis. Enhancement of NA mutagenesis by phenol and by spermine is due to the formation of unstable molecular species. We propose that reactive organic nitroso compounds are formed which then serve as delivery vehicles to promote mutagenicity of native DNA, perhaps via transnitrosation reactions. Similar reactions probably occur in vivo to promote NA-induced base substitution (but not frameshift) mutations in Salmonella typhimurium and in Escherichia coli. The possible significance of these observations to carcinogenesis is discussed.
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PMID:Nitrous acid mutagenesis of duplex DNA as a three-component system. 31 85

This review principally addresses a number of aspects of the occurrence and formation of the nitrosamines, highlighting principal areas of potential concern ranging from the spectrum of nitrosatable moieties found in the environment (e.g., secondary and tertiary amines, quaternary ammonium compounds, ureas, carbamates and guanidines), specific examples of nitrosamines found in food, alcoholic beverages, feed (and their significance for carcinogenesis bioassays), air and water. The factors influencing in vitro and in vivo nitrosation and the evidence for the latter in man are also discussed. Additionally, germane areas of the analysis of nitrosamines are reviewed with a focus on the major areas of concern and requirements of extreme sensitivity and selectivity in addition to the problems of artifacts in the analytical procedures.
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PMID:Overview of some aspects of occurrence, formation and analysis of nitrosamines. 38 8

Fiber is not digested by endogenous enzymes but is fermented by microbes principally in the large intestine. With fermentable energy available, microbes synthesize protein by using ammonia released by their enzymes from urea and other nitrogenous substances in ingesta and intestinal secretions. Fibber fermentation also yields fatty acids that lower the concentration of free ammonia by lowering pH. Fiber increases bulk and water of intestinal contents, shortens transit time, and decreases the concentration of toxic substances in contact with the intestinal mucosa. These processes decrease duration and intensity of exposure of the intestinal mucosa to free ammonia, the form of nitrogen that is most toxic and most readily absorbed by cells. At concentrations found in the lower bowel on usual Western diets, ammonia destroys cells, alters nucleic acid synthesis, increases intestinal mucosal cell mass, increases virus infections, favors growth of cancerous cells over noncancerous cells in tissue culture, and increases virus infections. Ammonia in the bowel increases as protein intake increases. The attributes of ammonia and the epidemiological evidence comparing populations that maintain low intakes of unrefined carbohydrate with those that consume high intakes of protein, fat, and refined carbohydrates implicate ammonia in carcinogenesis and other disease processes.
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PMID:Diet and cell growth modulation by ammonia. 70 76

The distribution of the 14C-labelled food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the tissues of C57B1/6 and NMRI mice was studied. The results showed a high and selective binding of radioactivity in the pigment epithelium of the eye and in the fur following a single dose (0.3-4 mg/kg) of [14C]PhIP in the pigmented C57B1/6 mice whereas no such localization of radioactivity was present in the albino NMRI mice. A low but selective covalent binding of radioactivity was observed in the liver, inner cortex of the kidney and in the tracheal mucosa of [14C]PhIP-injected mice. PhIP was firmly bound to synthetic melanin pigment in vitro; only 3% was released by extraction with a phosphate buffer (pH 7) whereas 72% was released by extraction by methanol:conc. NH3 (15:1). Three hours to 7 days following a single injection of [14C]PhIP in C57B1/6 mice the radioactivity in the eye was 3- to 6-fold higher than that in the liver or kidney. Almost 60% of the radioactive material present in the pigmented epithelium of the eye 3 and 24 h following injection could be extracted by basic methanol and identified as unchanged PhIP. The residual radioactivity in the pigmented epithelium of the eyes may represent a covalent binding of [14C]PhIP metabolites to cellular constituents or to a basic methanol-resistant binding of [14C]PhIP to melanin. The results indicate that pigmented tissues may be potential target tissues for the toxic effects of PhIP and suggest that the use of hair for biological monitoring of PhIP should be examined.
Carcinogenesis 1992 Dec
PMID:Binding of the food mutagen PhIP in pigmented tissues of mice. 147 32

Helicobacter pylori (HP) has been shown to possibly be a pathogen of gastric carcinoma. HP has urease activity and produces ammonia in the stomach. In this study, the role of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in rats. After 24 weeks pretreatment with MNNG (83 mg/l), 0.01% ammonia or tap water as a drinking water was administered for 24 weeks. The ammonia-treated rats showed a significantly higher incidence of gastric cancer (percent of animals with tumors and number of tumors per rat). Ammonia would thus appear to have an important role in HP-related human gastric carcinogenesis.
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PMID:Ammonia: a possible promotor in Helicobacter pylori-related gastric carcinogenesis. 151 5

Human hepatoma HEPG2 cells were infected with recombinant vaccinia virus vectors containing cDNAs encoding both known and variant rat cytochromes P450 (CYP). CYP2B1 and CYP2B2 cytochromes were equally well expressed (110-140 pmol/mg of microsomal protein) and catalyzed metabolism of 7,12-dimethylbenz[a]anthracene (DMBA). Their regioselectivity for DMBA metabolism paralleled that of the respective purified rat liver enzymes and reproduced previously reported regioselective differences between CYP2B1 and CYP2B2 [Wilson et al. (1984) Carcinogenesis 5, 1475-1483]. CYP2A1 and CYP2A2 expressed in HEPG2 microsomes exhibited nearly equal DMBA-metabolizing activities that closely matched that of purified CYP2A1. Although purified rat liver CYP2B1 was 3 times more active than purified rat liver CYP2B2, the expressed recombinant microsomal CYP2B1 (rCYP2B1) was 20 times less active than rCYP2B2, where activity matched that of the purified cytochrome. Microsomal suppression of rCYP2B1 catalytic activity was also observed for benzo[a]pyrene. Specific amino acid substitutions at equivalent positions of the completely homologous NH2-terminal halves of rCYP2B1 and rCYP2B2 changed this suppression effect. Thus, a L58----F, I114----F double mutant exhibited 3 times the normal activity for rCYP2B1 while remaining inhibitory for rCYP2B2. The single substitutions produced very different effects. The L58----F substitution prevented expression of rCYP2B1, while the I114----F substitution was inhibitory for both rCYP2B1 and rCYP2B2 (40 and 70%). A single E282----V mutation produced a stimulation of rCYP2B1 activity comparable to that of the L58----F, I114----F double substitution.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective suppression of the catalytic activity of cDNA-expressed cytochrome P4502B1 toward polycyclic hydrocarbons in the microsomal membrane: modification of this effect by specific amino acid substitutions. 154 25

It has been suggested that the endogenous nitrosation of aliphatic, cyclic and heterocyclic secondary amines in the urinary bladder of patients with chronic urinary bacterial infections and in the human stomach may provide an important additional source of exposure to carcinogenic volatile N-nitrosamines. The most commonly occurring nitrosatable secondary amines found in human saliva, gastric juice, blood, urine and faeces are dimethylamine (DMA), pyrrolidine (PYR) and piperidine (PIP). All of 40 analysed samples of gastric juice contained 0.87 +/- 0.89 (SEM) microgram/ml DMA, 39 contained 1.35 +/- 2.53 microgram/ml PIP, 36 contained 0.18 +/- 0.15 microgram/ml PYR and 14 contained 0.05 +/- 0.11 microgram/ml diethylamine. Nitrate (14.0 +/- 15.7 microgram/ml) was present in all samples and 11 of 40 samples contained 0.43 +/- 1.38 microgram/ml nitrite. Only one gastric juice sample with pH less than 4.5 contained nitrite (0.1 microgram/ml). In paraplegics, patients with bladder augmentations and two control groups without bacterial infections of the urinary bladder, a mean daily excretion of 40.5-49.7 mg/day DMA, 19.4-23.8 mg/day PYR and 26.1-31.7 mg/day PIP was found. In both patient groups suffering from chronic bacterial infection of the urinary bladder, the corresponding volatile N-nitrosamines were formed by endogenous nitrosation and excreted in urine.
Carcinogenesis 1992 Apr
PMID:Secondary amine precursors to nitrosamines in human saliva, gastric juice, blood, urine and faeces. 157 7

The cytosol fraction of J774-1 murine macrophages activated with lipopolysaccharide (LPS) + interferon-gamma (IFN-gamma) was found to nitrosate a wide range of secondary and tertiary amines. The reaction was dependent on L-arginine and NADPH. The optimal pH for nitrosation was 7.2-7.3. Nitrosation was inhibited by arginine derivatives such as NG-monomethyl-L-arginine and NG-nitro-L-arginine, well-known inhibitors of nitric oxide (NO) synthase. These results indicate that nitrosation is mediated by NO synthase, which catalyzes formation of NO and L-citrulline from L-arginine. Nitrosamine formation also required oxygen and was inversely correlated with the basicity of nitrosatable amines. The nitrosation was inhibited by oxyhemoglobin, an NO trapping agent, and enhanced by superoxide dismutase, which stabilizes NO. LPS + IFN-gamma induced approximately 500-600 times greater nitrosation activity than that of non-activated macrophages. Macrophages treated with LPS alone exhibited 3-4 times greater nitrosation activity than untreated macrophages, whereas macrophages treated with IFN-gamma alone did not show enhanced nitrosation activity. A combination of the cytosols from macrophages treated with LPS alone and IFN-gamma alone did not nitrosate morpholine as rapidly as the cytosol of macrophages treated with both compounds together. The activity for forming L-citrulline and nitrite/nitrate from L-arginine was markedly induced by treatment with either LPS alone or LPS + IFN-gamma but not with IFN-gamma. Those results suggest that some other factor(s) in addition to NO synthase is involved for efficient nitrosation by the macrophage cytosol. This factor(s) was not induced in macrophages by either LPS- or IFN-gamma alone, but was induced only in the presence of the two compounds.
Carcinogenesis 1991 Jul
PMID:L-arginine-dependent formation of N-nitrosamines by the cytosol of macrophages activated with lipopolysaccharide and interferon-gamma. 171 76

Twenty rats were randomized into a vesicosigmoidostomy and an unoperated control group. In both groups the 24 hour excretion of secondary amines, nitrate, nitrite and nitrosamines was measured before and after gavage of proline and nitrate, piperazine and nitrate, N-nitrosoproline, mono-N-nitrosopiperazine. The urinary nitrosamine concentrations were not significantly different between both groups neither before nor after application of the several substances. Thirty rats were randomized into two vesicosigmoidostomy groups with and without antibiotic coverage and an unoperated control group. After ligation of distal rectum and mesosigmoid the rectosigmoids were removed. No significant concentrations of volatile nitrosamines could be measured in the rectosigmoid contents of the three groups. One hundred and twenty rats randomized into three groups following vesicosigmoidostomy received the potential nitrosamine antidotes sodium-2-mercaptoethane sulfonate or sodiumpentosan-polysulfate or acted as controls. 12/118 (10.2%) developed adenomas and 25/118 (21.2%) adenocarcinomas at the vesico-colonic anastomosis with no significant differences between the three groups concerning tumor incidence or mortality. The results show that colon carcinomas occur in a rat model for ureterosigmoidostomy without evidence for thus induced nitrosamine formation. This and the missing effect of nitrosamine antidotes suggest that other factors than nitrosation must be responsible for colon carcinogenesis following urinary diversion via intestine.
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PMID:Tumor induction in a rat model for ureterosigmoidostomy without evidence of nitrosamine formation. 171 71


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