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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

Three-week-old female rats were fed 0.09 (zinc-deficient), 0.77 (zinc-adequate) or 3.98 (zinc-supplemented) mmol zinc/kg diet in three experimental groups and the palatal mucosa was painted with the water-soluble carcinogen 4-nitroquinoline N-oxide (4NQO) three times a week for 20 weeks. The zinc-supplemented diet seemed to retard the induction of carcinogenesis, whereas a low-zinc diet had the opposite effect. Once initial cellular changes had been induced the supplementary zinc seemed to accelerate their further advancement. Zinc-deficiency in animals fed a copper/zinc low-zinc diet was reflected in the plasma and liver zinc levels as well as in the copper/zinc ratio. The development of cancer was accompanied by a decrease in plasma zinc and an increase in the plasma copper/zinc ratio as well as in the liver zinc. These changes were most remarkable in the zinc-supplemented group.
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PMID:Influence of zinc on onset and progression of oral carcinogenesis in rats. 11 33

The rate of ethylation of t-RNA in vivo by L-ethionine[ethyl-1-14C] markedly lowered in the liver of rats fed a diet containing copper than that of control. In corporation of the labeled compound into the t-RNA of liver by a single injection. of L-ethionine[ethyl-1-14C] was inhibited as much as 50% by the preceding concurrent administration of copper and ethionine added in the diet to rats. Direct interaction of copper ion with ethylation by ethione in the specific t-RNA of the rat liver was examined as an important biochemical explanation in molecular level for the inhibitory mechanism of copper on rat liver carcinogenesis by ethionine. Profiles of normal t-RNA on methylated albumin-kieselguhr column chromatography revealed three components for leucine, two of which were found at the tube number 40 to 50 and disappeared in the leucyl t-RNA treated with ethionine. The components for leucine that disappeared were normalized in the liver of rats by the concurrent administration of copper.
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PMID:Mechanism of suppressive effect of basic cupric acetate on rat liver carcinogenesis by ethionine. 96 57

The activities of several flavonoids and the related nonflavonoid compound epicatechin were compared with respect to Cu(II)-induced strand scission of DNA by using two different assays. The same series of compounds was used to study the stoichiometry of Cu(II) reduction in the absence of DNA. The compounds were compared for their ability to generate superoxide, hydrogen peroxide and the Cu(II)-dependent production of hydroxyl radicals. Flavonoids were examined to assess the production of a charge-transfer complex with Cu and the rate of decay of the complexes were compared. All the compounds tested had some ability to cause DNA strand scission in the presence of Cu(II), with myricetin being the most active and galangin the least active. The ability to cause such scission correlated with the rate of decay of the charge-transfer complex, the ability to generate active oxygen species and with the stoichiometry of Cu(II) binding. Analysis of the data in the light of the structural differences between the flavonoids led to a discussion of alternative Cu(II)-sequestering mechanisms.
Carcinogenesis 1992 Apr
PMID:Activities of flavonoids for the cleavage of DNA in the presence of Cu(II): correlation with generation of active oxygen species. 131 26

The present study demonstrates that biogenic silica fibers (BSF), previously shown to promote skin tumors in mice and more recently to promote the induction of mesotheliomas when injected into the pleural cavity of rats, rapidly induces epidermal ornithine decarboxylase (ODC) activity in SENCAR mice following topical application. The time course for induction of epidermal ODC by BSF was very similar to that observed following topical treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). Maximal ODC activity was observed 4-6 h following treatment with BSF. Cycloheximide (70 mg/kg i.p.) partially inhibited (61%) the induction of ODC by BSF at 5 h. In addition, retinoic acid (RA, 5 micrograms per mouse given 30 min before BSF) effectively inhibited BSF-induced ODC by 68%, while indomethacin (100 micrograms per mouse 2 h before BSF) had little or no effect. Copper(II) bis(diisopropylsalicylate) (2 mumol 30 min before BSF), an effective inhibitor of TPA-induced ODC activity and tumor promotion, also had little or no effect on BSF-induced ODC. The work described in this paper suggests that BSF induces epidermal ODC by a very specific mechanism that exhibits both similarities and differences with that of the phorbol ester, TPA. Nevertheless, this response strongly supports the conclusion that BSF is an effective tumor promoter in mouse skin and that ODC induction is an integral part of the mechanism of action of this environmental promoter.
Carcinogenesis 1992 Apr
PMID:Induction of epidermal ornithine decarboxylase activity in mouse skin exposed to biogenic silica fibers. 131 27

Pulsed field gel electrophoresis showed that caffeic acid induced DNA strand breaks in cultured human cells in the presence of Mn(II). With alkali treatment, DNA single-strand breaks were observed. The strand breakage was increased by the treatment of buthionine sulphoximine (a GSH synthesis inhibitor) and 3-aminotriazol (a catalase inhibitor) and decreased by catalase, indicating the involvement of H2O2. The DNA damage was decreased by o-phenanthroline, indicating the involvement of transition metal ion. Damage to isolated DNA from c-Ha-ras-1 protooncogene was investigated by a DNA sequencing technique. Caffeic acid caused DNA damage in the presence of Cu(II) but not in the presence of either Mn(II) or Fe(III). Caffeic acid plus Cu(II) induced piperidine-labile sites frequently at thymine residues, especially of the 5'-GTC-3' and 5'-CTG-3' sequences. Typical OH scavengers showed no inhibitory effects. The inhibitory effects of bathocuproine and catalase on Cu(II)-mediated DNA damage suggest that Cu(I) and H2O2 have important roles in the production of active species causing DNA damage. The Cu(II)-mediated DNA damage was enhanced by pre-incubation of caffeic acid with Mn(II). Mn(II)- or Cu(II)-catalyzed autoxidation of caffeic acid produced H2O2 with efficiency of Mn(II) greater than Cu(II). These results suggest that in the presence of Mn(II) or Cu(II), caffeic acid produces H2O2, which is activated by transition metals to cause damage to DNA in vitro and probably in cultured cells.
Carcinogenesis 1992 Sep
PMID:Caffeic acid causes metal-dependent damage to cellular and isolated DNA through H2O2 formation. 139 30

The entrapment of heterocyclic aromatic amine gastrointestinal (GI) carcinogens (HAAs), by retrievable semipermeable magnetic polyethylenimine (PEI) microcapsules was investigated in vitro and in vivo as an approach for human biomonitoring. Previous studies showed that PEI microcapsules successfully entrapped benzo[a]pyrene (B[]P) and its metabolites in the GI tract of rodents. In this study, we have shown that 14C-labelled 2-amino-3-methylimidazo[4,5f]quinoline (IQ), 2-amino-1-methylphenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-6-methyldipyrido[1,2-a:3'2'-d]imidazole (Glu-P-1) are adsorbed to PEI microcapsules in vitro and can be desorbed by treatment with ammoniac methanol. Binding of HAAs to PEI microcapsules containing copper phthalocyanine (TCPTS), a moiety which reversibly binds chemicals with aromatic planar structures, was 2- to 4-fold higher than with unmodified PEI microcapsules. PEI microcapsules also acted as a nucleophile and trapped the proximate carcinogenic metabolite of IQ, 2-hydroxy-amino-3-methyl-imidazo[4,5f]quinoline (N-hydroxy-IQ). The entrapment of 14C-labelled IQ and PhIP by microcapsules was investigated in vivo in male F344 rats fed a conventional chow diet or a human diet with varying amounts of fat and beef intake typically consumed in the UK. Animals were adapted to human diets which were either high (H) or low (L) in fat (F), beef protein (B) and dietary fibre non-starch polysaccharide (NSP). Microcapsule entrapment of IQ and metabolites was 0.5-2.0% of the dose and 4-fold higher in rats consuming a HF/HB/LNSP than those consuming a LF/LB/HNSP diet, these being respectively putatative high- and low-risk-associated diets. In the HF/HB/LNSP diet group, a higher amount of IQ metabolites were detected in the microcapsules; a lower proportion of covalently bound metabolites could be removed by acid hydrolysis. Urinary excretion was 2-fold greater and analysis of the urinary metabolites showed there to be lower sulfotransferase activity than in the LF/LB/HNSP group. The amount of 14C-labelled PhIP entrapped by PEI microcapsules was 1.5% of the dose in rodents fed a LF/HB/LNSP human diet and binding was 7-fold higher than in rodents fed a semi-purified diet. These results demonstrate that microcapsules can entrap IQ and PhIP and their metabolites within the GI tract of rodents. The amounts entrapped by microcapsules in the rodent model suggests that this approach may be feasible for human biomonitoring of HAAs and for non-invasively studying dietary modulations of carcinogen exposure within a potential HAA target organ at high risk from as-yet unidentified causes.
Carcinogenesis 1992 Dec
PMID:Entrapment by magnetic microcapsules of the protein pyrolysates IQ, PhIP and Glu-P-1, and alteration of IQ metabolite exposure within the rat gastrointestinal tract by risk-modulating components of the human diet. 147 44

The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early-stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N-hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not.
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PMID:Promoting effects of potassium dibasic phosphate on early-stage renal carcinogenesis in unilaterally nephrectomized rats treated with N-ethyl-N-hydroxyethylnitrosamine. 151 46

The effects of ascorbic acid and curcumin on quercetin-induced DNA damage, lipid peroxidation protein degradation were investigated in a model system of isolated rat-liver nuclei under aerobic conditions and in the presence of equimolar concentrations of iron or copper. Neither ascorbic acid nor curcumin inhibited quercetin-induced nuclear DNA damage, lipid peroxidation, or protein degradation. In fact, both antioxidants stimulated the oxidative damage to nuclear macromolecules. Ascorbic acid significantly increased the quercetin-induced nuclear DNA damage in the presence of either iron or copper. The increases in quercetin-induced nuclear lipid peroxidation and protein degradation by ascorbic acid were statistically significant only in the presence of iron or copper, respectively. Similarly, stimulation of quercetin-induced DNA damage and lipid peroxidation by curcumin was statistically significant only in the presence of copper or iron, respectively. Curcumin had no significant effect on nuclear protein degradation. These results demonstrate the pro-oxidant properties of ascorbic acid and curcumin, compounds that also demonstrate antioxidant and anticarcinogenic properties. Ascorbic acid and curcumin may therefore each have a dual role in carcinogenesis.
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PMID:Effect of ascorbic acid and curcumin on quercetin-induced nuclear DNA damage, lipid peroxidation and protein degradation. 157 92

Chlorophyllin (CHL), the water soluble sodium/copper salt of chlorophyll, was investigated for its effect on colorectal cancer risk in the rat-dimethyldrazine colon carcinogenesis model. Ninety weanling Fisher 344 male rats were treated with five weekly injections of 1,2 dimethylhydrazine (DMH), 20 mg base/kg body weight. Rats had been previously divided into three groups, consuming either rat chow and water (Group I), rat chow and CHL 1.5 mM in water throughout the experiment (Group II), or water and rat chow during DMH injection, adding CHL 1.5 mM to the drinking water after completion of the DMH treatments. At sarcifice, the incidence and yield of colorectal tumors were as follows: Group I 10% and 0.1; Group II, 23% and 0.27; and Group III, 47% and 0.53 (p less than 0.005 for incidence and = 0.003 for yield). These data demonstrate that, though it is well established that CHL is an antimutagen, CHL in this colorectal carcinogenesis model acted as a tumor promoter.
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PMID:Chlorophyllin, an antimutagen, acts as a tumor promoter in the rat-dimethylhydrazine colon carcinogenesis model. 162 32


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