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

General behavioral patterns of rats or mice fed 5 wt% safflower oil (75% linoleate [n-6] and less than 0.1% alpha-linolenate [n-3]) for two generations were significantly different from those of animals fed 5 wt% perilla oil (15% n-6 and 55% n-3). Also, brightness-discrimination learning ability and retinal function were higher in the perilla group than in the group fed 5 wt% soybean oil (53% n-6 and 4.7% n-3) or safflower oil, indicating that the requirement of n-3 for the maximum responses of the nervous system is above 0.6 en% when there is 6.8 en% linoleate n-6. Perilla oil has been found to be beneficial for the suppression of carcinogenesis, allergic hyperreactivity, thrombotic tendency, apoplexy, hypertension, and aging in animals, as compared with soybean oil and safflower oil. These results are against a lipid peroxide theory of aging, carcinogenesis, and chronic diseases. Animal experiments and epidemiological studies lead to a recommendation that the intake of n-6 should be decreased to as low as 2-4 en% and that of n-3 be increased to levels higher than linoleate n-6 for the prevention of chronic diseases prevailing in the industrialized countries.
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PMID:Minimum requirements of n-3 and n-6 essential fatty acids for the function of the central nervous system and for the prevention of chronic disease. 157 78

The possibility that the interaction of C-nitroso aromatics with polyunsaturated fatty acids (PUFA) causes lipid peroxidation was investigated through determination of conjugated diene and malodialdehyde (MDA) formation after anaerobic/aerobic vs. aerobic incubations of nitrosobenzene (NOB) or 2-nitrosofluorene (2-NOF) with linoleic, linolenic or arachidonic acid or methyl linolenate. Anaerobic incubation of NOB or 2-NOF with linolenic acid at the molar ratio of 1:1 for 24 h yielded approximately 5.5-13% of the PUFA as conjugated diene which appeared stable upon exposure to air. Interaction of PUFA and 2-NOF or NOB yielded MDA, the amounts of which were significantly greater when 24-h anaerobic preceded 1-6-h aerobic incubation. Furthermore, the differences in the amounts of MDA resulting from 24- and 0-h anaerobic incubations were significantly greater when the molar ratio of 2-NOF (or NOB) to PUFA was increased (2.0 greater than 1.0 greater than 0.5). Superoxide dismutase or catalase had no effect on the yields of MDA following either anaerobic/aerobic or aerobic incubations of PUFA and 2-NOF. EDTA (1 or 10 microM) had no effect on the yields of MDA from aerobic incubations, but it decreased the amounts of MDA (by approximately 30 or 60%, respectively) from anaerobic/aerobic incubations. The data suggested that inhibition by EDTA was due to chelation of trace iron, which following anaerobic interaction of PUFA and 2-NOF might have been reduced to Fe2+ and contributed to the enhanced lipid peroxidation. Thus, adduction of C-nitroso aromatics to PUFA yields radical species which directly and/or via reaction with trace iron lead to lipid peroxidation. The lipophilicity of C-nitroso aromatics suggests that this process may be of consequence in their mutagenesis/carcinogenesis.
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PMID:Interaction of C-nitroso aromatics with polyunsaturated fatty acids: route to lipid peroxidation. 189 3

Promotion of carcinogenesis in rats by dietary fat depends on the amount and type of fatty acids ingested, mainly as triglycerides. A certain amount of essential fatty acid of the linoleate type (n-6) is required for promotion of mammary cancer and pancreatic cancer and probably also for colon cancer. Promotion is also enhanced by a high level of dietary fat, and this additional effect seems to be relatively independent of the type of fat. Saturated fatty acids, either medium or long chain, and cis and trans monoenoic fatty acids appear to have no specific promoting effects. Fish oils containing long-chain polyunsaturated fatty acids of the linolenate type (n-3) are inhibitory, and this may also be true for rapeseed oil high in erucic acid, a long-chain monoenoic fatty acid. The promoting action of dietary fat can be modified by other components of the diet, such as starch, sugar, and fiber. Promotion is also dependent on the length of time animals are exposed to the high-fat diet. The overall tumor yield can be decreased by reducing the level and degree of unsaturation of the dietary fat after a period of feeding a high polyunsaturated-fat diet.
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PMID:Summation: which fat/how much fat--animals. 362

The first evidence that dietary fat influences mammary carcinogenesis was provided by Tannenbaum, who showed that mice fed a high-fat diet developed spontaneous tumors more readily than those fed a low-fat diet. Similar observations have been made with various other animal models. Polyunsaturated vegetable oils enhance carcinogenesis more effectively than saturated fats, because of their higher linoleate content. Diets containing high levels of polyunsaturated fish oils do not stimulate carcinogenesis, however, perhaps because their polyunsaturated fatty acids belong mainly to the linolenate family. Dietary fat acts primarily as a promoting agent, but the exact mechanism is still unclear. The requirement for linoleate and the fact that the fat effect can be blocked by prostaglandin biosynthesis inhibitors suggests that it may be mediated by biologically-active compounds derived from linoleate. Other possibilities include changes in hormonal balance, alterations in the fatty acids of membrane lipids, effects on the immune system, modulation of intercellular communications, and metabolic alterations related to differences in fat and caloric intake. Interest in the role of dietary fat in mammary carcinogenesis has been greatly stimulated by epidemiological evidence of a strong, positive correlation between breast cancer and dietary fat. In these epidemiological data, total dietary fat shows a better correlation than fat from either plant or animal sources individually, and there is no apparent correlation with the polyunsaturated fatty acid content of the diet. Further studies are needed to investigate more thoroughly this apparent difference between experimental and epidemiological data.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary fat in relation to mammary carcinogenesis. 391 97

High-fat diets enhance the development of mammary and intestinal tumors on animals, and dietary fat also shows a strong positive correlation with mortality from cancers of the breast and colon in human populations. In animals, dietary fat appears to act as a promoter of carcinogenesis rather than as an influence in the initiation of tumors. Polyunsaturated fats enhance mammary tumorigenesis and stimulate tumor growth more effectively than do saturated fats. However, diets containing a small amount of polyunsaturated fat and a high level of saturated fat increase mammary tumor yields as effectively as do diets containing a high level of polyunsaturated fat. Fatty acids of either the linoleate or linolenate family appear to be able to satisfy the small requirement for polyunsaturated fat. The mechanism by which dietary fat influences mammary tumorigenesis is not known but may involve hormonal effects, immune responses, to alterations in cellular membranes. Dietary fat is thought to enhance the development of intestinal tumors by stimulating production of bile acids, some of which act as promoters of tumorigenesis.
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PMID:Neutral fats and cancer. 726 Sep 26

Oxidative damage caused by potassium bromate (KBrO3), a rat renal carcinogen, was investigated using in vitro preparations of rat renal proximal tubules (RPT) and renal nuclear fractions. Release of lactate dehydrogenase and decrease of SH-group content in RPT (1 mg protein/ml) by KBrO3 (0.5-5 mM) in a concentration- and time-dependent manner were observed. Peroxidized arachidonic acid and 8-hydroxydeoxyguanosine (8-OH-dG) levels in RPT were increased after administration of 2 and 5 mM KBrO3. 8-OH-dG formation was observed after incubation of renal nuclei with a lipid-peroxiding system, autooxidized methyl linolenate, or KBrO3. These findings provide support for involvement of lipid peroxidation in producing oxidized DNA damage by KBrO3 directly to RPT, the target site for renal carcinogenesis.
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PMID:Oxidative DNA damage induced by potassium bromate in isolated rat renal proximal tubules and renal nuclei. 795 62

Despite data favouring a role of dietary fat in colonic carcinogenesis, no study has focused on tissue n3 and n6 fatty acid (FA) status in human colon adenoma-carcinoma sequence. Thus, FA profile was measured in plasma phospholipids of patients with colorectal cancer (n = 22), sporadic adenoma (n = 27), and normal colon (n = 12) (control group). Additionally, mucosal FAs were assessed in both diseased and normal mucosa of cancer (n = 15) and adenoma (n = 21) patients, and from normal mucosa of controls (n = 8). There were no differences in FA profile of both plasma phospholipids and normal mucosa, between adenoma and control patients. There were considerable differences, however, in FAs between diseased and paired normal mucosa of adenoma patients, with increases of linoleic (p = 0.02), dihomogammalinolenic (p = 0.014), and eicosapentaenoic (p = 0.012) acids, and decreases of alpha linolenic (p = 0.001) and arachidonic (p = 0.02) acids in diseased mucosa. A stepwise reduction of eicosapentaenoic acid concentrations in diseased mucosa from benign adenoma to the most advanced colon cancer was seen (p = 0.009). Cancer patients showed lower alpha linolenate (p = 0.002) and higher dihomogammalinolenate (p = 0.003) in diseased than in paired normal mucosa. In conclusion changes in tissue n3 and n6 FA status might participate in the early phases of the human colorectal carcinogenesis.
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PMID:Changes of the mucosal n3 and n6 fatty acid status occur early in the colorectal adenoma-carcinoma sequence. 899 64

Conjugated linoleic acid (CLA) is a chemoprotective fatty acid that inhibits mammary, colon, forestomach, and skin carcinogenesis in experimental animals. We hypothesize that the ubiquitous chemoprotective actions of dietary CLA in extrahepatic tissues are dependent upon its role in modulating fatty acid composition and metabolism in liver, the major organ for lipid metabolism. This study begins to evaluate the role of CLA in lipid metabolism by determining the modulation of fatty acid composition by CLA. Female SENCAR mice were fed semipurified diets containing 0.0% (Diet A), 0.5% (Diet B), 1.0% (Diet C), or 1.5% (Diet D) CLA (by weight) for six weeks. Mice fed Diets B, C, and D exhibited lower body weights and elevated amounts of extractable total lipid in livers compared with mice fed diets without CLA (Diet A). Analyses of the fatty acid composition of liver by gas chromatography revealed that dietary CLA was incorporated into neutral and phospholipids at the expense of linoleate in Diets B, C, and D; oleate increased and arachidonate decreased in neutral lipids of CLA diet groups. In addition, increasing dietary CLA was associated with reduced linoleate in hepatic phospholipids. In an in vitro assay, CLA was desaturated to an unidentified 18:3 product to a similar extent as linoleate conversion to gamma-linolenate (9.88, and 13.63%, respectively). These data suggest that CLA may affect metabolic interconversion of fatty acids in liver that may ultimately result in modified fatty acid composition and arachidonate-derived eicosanoid production in extrahepatic tissues. In addition to determining how dietary CLA modulates eicosanoid synthesis, further work is needed to identify enzymatic products that may result from desaturation of CLA.
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PMID:Conjugated linoleic acid modulates hepatic lipid composition in mice. 907 11

Ethanol consumption is a high risk factor for oesophageal carcinoma and studies indicate that it acts as a promoter of N-nitrosomethylbenzylamine (NMBzA)-induced oesophageal carcinogenesis. The studies described here indicate that ethanol-induced promotion was related with an increase in indices of lipid peroxidation in the target oesophageal tissue and that such an increase was associated with significant changes in the fatty acid profile of phospholipids. Young Sprague-Dawley rats were treated with NMBzA, 2.5 mg/kg body weight, three times a week for 3 weeks, and a week afterwards fed a 7% ethanolic diet that was continued until their death at 10 months. Cumulative ethane exhaled by rats was measured a week before their death and was found to increase significantly with NMBzA treatment but more so when followed by ethanol consumption. Cholesterol, phospholipids, and some indices of lipid peroxidation were measured in the oesophagus and liver. Whereas the levels of cholesterol and phospholipids were not affected in control-fed rats with or without the NMBzA treatment, ethanol consumption by either the untreated or NMBzA-treated rats caused a significant increase in the targeted oesophagus as well as the liver, the major site of ethanol and carcinogen metabolism. Ethanol consumption also increased all the indices of lipid peroxidation, i.e. malondialdehyde, lipid fluorescence, diene- and triene-conjugates; the largest increases were observed in rats that received both NMBzA and ethanol. A comparison of the fatty acid profile of phospholipids from the oesophagus and liver indicated significant alterations both with the NMBzA treatment and ethanol consumption. However, the fatty acid profile with regard to its peroxidability was significantly modified only with ethanol consumption and only in the oesophagus of the NMBzA-treated or untreated rats. Also, hepatic phospholipids showed a substantial increase in linolenate and no change in arachidonate, but the oesophageal phospholipids exhibited a pronounced increase in the levels of C18:3, C20:2, C20:3, C20:3' and C22:6 with a significant increase in arachidonate when use of ethanol followed the NMBzA treatment, suggesting a disorder in lipid and eicosanoid metabolism. We propose that ethanol may promote carcinogenesis through excessive cell proliferation induced by disordered lipid and eicosanoid metabolism that may cause a selective outgrowth of the initiated cells.
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PMID:Ethanol-mediated promotion of oesophageal carcinogenesis: association with lipid peroxidation and changes in phospholipid fatty acid profile of the target tissue. 919 22

Freeze-dried black raspberries (BRBs) have demonstrated chemopreventive effects in a dietary intervention trial with human colorectal cancer patients. The aim of this study was to investigate BRB-caused metabolite changes using the Apc(Min/+) mouse as a model of human colorectal cancer. Wild-type (WT) mice were fed control diet, and Apc(Min/+) mice were fed either control diet or control diet supplemented with 5% BRBs for 8 weeks. Colonic and intestinal polyp size and number were measured. A non-targeted metabolomic analysis was conducted on colonic mucosa, liver and fecal specimens. Eight weeks of BRB treatment significantly decreased intestinal and colonic polyp number and size in Apc(Min/+) mice. The apc gene mutation significantly changed 52 metabolites in colonic mucosa associated with increased amino acid and decreased lipid metabolites, as well as 39 liver and 8 fecal metabolites. BRBs significantly reversed 23 apc-regulated metabolites, including 13 colonic mucosa, 8 liver and 2 fecal metabolites that were involved in amino acid, glutathione, lipid and nucleotide metabolism. Of these, changes in eight metabolites were linearly correlated with decreased colonic polyp number and size in BRB-treated Apc(Min/+) mice. Elevated levels of putrescine and linolenate in Apc(Min/+) mice were significantly decreased by BRBs. Ornithine decarboxylase expression, the key enzyme in putrescine generation, was fully suppressed by BRBs. These results suggest that BRBs produced beneficial effects against colonic adenoma development in Apc(Min/+) mice and modulated multiple metabolic pathways. The metabolite changes produced by BRBs might potentially reflect the BRB-mediated chemopreventive effects in colorectal cancer patients.
Carcinogenesis 2015 Oct
PMID:Black raspberries suppress colonic adenoma development in ApcMin/+ mice: relation to metabolite profiles. 2624 25


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