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

Intestinal exposure to ingested iron may be a principal determinant of human colorectal cancer risk. Evidence exists associating iron with both the initiating and promoting phases of carcinogenesis as well as somatic defenses against early cancers through hypoferremia (progression or proliferation). Iron intake and the ingestion of associated foods that greatly affect iron bioavailability and absorption (phytate, tannin, ascorbate, and alcohol) vary widely between high-risk and low-risk countries as well as within the United States. These variances in intake may explain not only the gradients in risk between populations, but the crossover in risk between sexes related to age within the United States. Human and rodent studies support the above hypothesis and are reviewed herein, however they are few in number and in many cases lack key data.
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PMID:Dietary iron and colorectal cancer risk. 155 19

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

Reactive oxygen species can give rise to numerous modifications of DNA. We have investigated the formation of such modifications using the nuclease P1 digestion method of the 32P-postlabelling procedure for the detection of DNA damage. Analysis of DNA that had been treated with a Fenton-type system of copper (or iron) ions and H2O2 resulted in the detection of up to ten discrete 32P-labelled spots, displaying chromatographic characteristics similar to aromatic adducts, on PEI-cellulose TLC. Maximum total levels equivalent to 28 adducts/10(8) nucleotides were achieved after 15 min of treatment with Cu2+/H2O2. The formation of adducts was 1.5 times greater if single-stranded rather than double-stranded DNA was employed, suggesting an intrastrand effect. Experiments with 3'-deoxyribonucleotides demonstrated that the adducts detected did not represent base modifications such as 8-hydroxydeoxyguanosine or thymidine glycols. However, treatment of specific dinucleotides (dApdG and dApdA) was found to produce two major adducts that were chromatographically identical by TLC and HPLC to the two major adducts formed in DNA. It is proposed that these species with aromatic adduct-like characteristics are the result of the intrastrand linking of specific adjacent bases in DNA.
Carcinogenesis 1992 Jul
PMID:Detection and characterization by 32P-postlabelling of DNA adducts induced by a Fenton-type oxygen radical-generating system. 163 78

Effects of dietary iron deficiency on inductions of putative preneoplastic lesions and oxidative alterations in the livers of rats by a choline-deficient L-amino acid defined (CDAA) diet were examined. Male Fischer 344 rats, 4 weeks old, were used with a total experimental period of 16 weeks, consisting of 4-week pretreatment and 12-week treatment periods (periods A and B respectively). During period A, a choline-supplemented L-amino acid defined (CSAA) or an iron-deficient CSAA diet was administered, and the CDAA or an iron-deficient CDAA diet was fed in period B. Formation of 8-hydroxydeoxyguanosine (8OHdG), a DNA adduct generated by activated oxygen species, in DNA and lipid peroxidation in liver cell membranes were sequentially determined after the beginning of period B. At the end of the experiment, development of gamma-glutamyltransferase (GGT) and glutathione S-transferase placental form (GSTP) positive liver lesions were quantitatively analysed. In the animals fed the CDAA diet, formation of 8OHdG and lipid peroxidation increased with time, and GGT and GSTP positive liver lesions developed. Formation of 8OHdG, lipid peroxidation and the numbers of induced enzyme-altered liver lesions were all reduced in rats fed the iron-deficient CSAA diet in period A and/or the iron-deficient CDAA diet in period B. The present results indicate that iron plays an important role in induction of preneoplastic liver lesions in rats caused by exposure to the CDAA diet possibly in connection with its known catalytic role in generation of highly reactive activated oxygen species.
Carcinogenesis 1992 Jul
PMID:Inhibitory effect of dietary iron deficiency on inductions of putative preneoplastic lesions as well as 8-hydroxydeoxyguanosine in DNA and lipid peroxidation in the livers of rats caused by exposure to a choline-deficient L-amino acid defined diet. 163 91

Iron exclusion has been used to identify foci of hepatocellular alteration (FHA) in rats exposed to known carcinogens. This study investigates whether basophilic FHA occurring spontaneously in aged female Fischer 344 rats also exclude iron. Female rats 514-544 days of age were given supplemental iron by injection for 2 weeks prior to being killed. Serial sections of the liver stained with hematoxylin and eosin or Gomori's stain were examined. Seventy-five basophilic FHA were identified; none excluded iron. It may be possible to differentiate spontaneous basophilic FHA from carcinogen-induced, iron-excluding FHA by the use of this staining method.
Carcinogenesis 1990 Dec
PMID:Spontaneous basophilic foci of hepatocellular alteration in Fischer 344 female rats do not exclude iron. 170 70

Inducibility of oxidative stress in rat liver in vivo by menadione-associated redox cycling activation under redox enzyme modulating conditions was examined by monitoring hepatocyte injury and 8-hydroxydeoxyguanosine (8-OHdG) levels of liver DNA. In addition, the treatment-associated liver tumor initiating activity was assessed in terms of development of gamma-glutamyl-transpeptidase (GGT)- and glutathione S-transferase placental form (GST-P)-positive foci and hyperplastic nodules. With or without following menadione treatment (50 mg/kg, i.g.), redox enzyme modulations of increased cytochrome P450 reductase activity induced by phenobarbital (PB)-Na (100 mg/kg, i.p. for 5 days), inhibition of DT-diaphorase by dicumarol (25 mg/kg, i.p.) and depletion of glutathione by phorone (200 mg/kg, i.p.), with or without further supplement of iron EDTA-Na-Fe(III) (70 mg/kg, i.p.), caused both substantial hepatocyte necrosis and 8-OHdG production in Fischer 344 male rats. Subsequent feeding with a 0.05% PB diet for 64 weeks resulted in slightly increased development of GGT-positive foci but not GST-P positive lesions or hyperplastic nodules, suggesting a lack of tumor-initiating activity of the oxidative DNA damage associated with redox enzyme modulations with or without menadione.
Carcinogenesis 1991 Apr
PMID:Induction of 8-hydroxydeoxyguanosine but not initiation of carcinogenesis by redox enzyme modulations with or without menadione in rat liver. 170 52

Treatment of Ah-responsive C57BL/10ScSn mice with iron greatly sensitizes them to induction of hepatic porphyria and tumour formation by the polychlorinated biphenyl mixture Aroclor 1254. In the present studies, male C57BL/10ScSn mice received a single dose of iron-dextran (600 mg Fe/kg) and were fed a diet containing 0.01% Aroclor 1254 for 1, 3 and 5 weeks. By use of HPLC with electrochemical detection, 8-hydroxydeoxyguanosine (8-OHdG) was then measured in liver DNA as a marker for oxidative damage. Treatments with iron or Aroclor alone did not result in a significant increase in 8-OHdG except at 3 weeks following iron treatment. At 1 and 3 weeks 8-OHdG levels were induced approximately 3- and 5-fold above control groups respectively in iron- and Aroclor-treated animals. Although there was an apparent 5- to 10-fold increase in the level of 8-OHdG at 5 weeks, this was partially attributed to the in vitro effects of porphyrins, levels of which were massively elevated in liver at this time point. The iron/Aroclor-induced synergistic elevation of 8-OHdG at 1 and 3 weeks was concluded to be due to in vivo damage, thus suggesting the importance of DNA oxidation in the early events of carcinogenesis in this system.
Carcinogenesis 1992 Feb
PMID:Induction of 8-hydroxydeoxyguanosine in Ah-responsive mouse liver by iron and Aroclor 1254. 174 15

Free radicals, intermediates in the tissue damage caused by radiation, are formed, inter alia, in interactions catalyzed by iron, which synergizes with radiation and some cytostatics (anthracyclins) in causing cell damage. Conversely, iron chelators can counteract cell damage. Similarly, antioxidants can slow atherogenesis, caused in part by oxidative stress and free radicals. Cell damage is also prevented by physiological defense systems like superoxide dismutase, against endogenous free radicals formed by granulocytes, monocytes, etc. Iron can thus induce free radicals which cause DNA double strand breaks and oncogene activation. This is suggested by four epidemiological studies suggesting a higher cancer risk in patients with larger iron stores than in those with small iron stores. In addition to its effect on carcinogenesis, iron can also maintain the growth of malignant cells as well as growth of pathogens. Breast cancer cells, for instance, display 5-15 times more transferrin receptors than normal breast tissue. Iron-carrying transferrin is in fact a growth factor. Hyposideremia in patients with cancer or infection is not a paraphenomenon but a functioning defense mechanism ('nutritional immunity'). If this immunity is broken by iron administration, relapses of diseases like tuberculosis, brucellosis, and malaria have been described. While iron-deficiency anemia should of course be diagnosed, treated and if possible prevented, there are good reasons to avoid over-utilization of medicamental iron.
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PMID:Iron, free radicals and cancer. 182 Apr 88

The generation of free radicals by microsome-mediated redox cycling between catechol estrogens or diethylstilbestrol and their corresponding quinones has previously been demonstrated in vitro. However, the reaction of free radicals with DNA has not yet been detected in animals treated with estrogen and is the subject of this investigation. The reaction of guanine bases of DNA with hydroxyl radicals to form 8-hydroxydeoxyguanosine has been used as a monitor of free radical generation in kidney and liver of Syrian hamsters, a species prone to estrogen-induced carcinogenesis. Prior to in vivo measurements, the in vitro hydroxylation of guanine bases of DNA under conditions of redox cycling of estrogen was investigated. In incubations of DNA or deoxyguanosine with hamster kidney microsomes, NADPH, and diethylstilbestrol 4',4"-quinone, the hydroxylation of guanine bases of free deoxyguanosine or of DNA was 50 to 100% higher than in controls. When incubations were carried out in the presence of iron(III) chloride, the hydroxylation of guanine bases was 2.5- or 10-fold higher than control values. There was a 65% increase from control values in levels of 8-hydroxydeoxyguanosine in liver DNA of hamsters treated with 20 mg/kg/day diethylstilbestrol for 3 days and 100 mg/kg on the 4th day. In hamsters treated chronically with diethylstilbestrol implants for 15 days, 8-hydroxydeoxyguanosine levels more than doubled from control values in kidney but not liver DNA. Treatment of hamsters with estradiol for various time periods did not induce any changes in levels of hydroxylated guanine in either kidney or liver. It was concluded that in vitro and in vivo redox cycling of diethylstilbestrol hydroxylated guanine bases in DNA.
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PMID:Elevated 8-hydroxydeoxyguanosine levels in DNA of diethylstilbestrol-treated Syrian hamsters: covalent DNA damage by free radicals generated by redox cycling of diethylstilbestrol. 185 6

Oxidative damage to proteins is known to occur via conversion of side chain amino groups to corresponding carbonyl derivatives. Such damage to enzymes and purified proteins has been quantified previously by reduction with sodium boro[3H]hydride and subsequent measurement of the incorporation of 3H into amino acid fractions. In this study, the NaB3H4 reduction assay was modified to permit the quantitation of free radical-mediated oxidative damage to proteins obtained from animals. Modifications included additional extractions of protein isolates with organic solvents to remove lipids and with nitric acid to remove metal ions. The modified assay has first been validated in vitro by measuring changes in levels of oxidative damage to bovine serum albumin exposed to xanthine plus xanthine oxidase (2-fold increase), to hydrogen peroxide and iron(II) sulfate (5-fold increase), or to gamma radiation (30-fold increase over controls, respectively). gamma radiation of isolated hamster kidney protein also raised the carbonyl content in a dose-dependent manner. The modified assay has then been validated in vivo by measuring the changes in oxidative damage to lung tissue in animals exposed to approximately 85% oxygen (2-fold increase) or to different doses of paraquat (5-fold increase with the high dose over controls, respectively). The assay was then used to examine free radical-mediated oxidation introduced by acute or chronic treatment of hamsters with estrogens, since both synthetic and natural estrogens induce kidney tumors in this species. Priming of hamsters for 3 days with 20 mg/kg/day diethylstilbestrol and treatment with 100 mg/kg of this drug on the 4th day resulted in a 160% increase in free radical modification of renal proteins. Oxidative damage to kidney proteins was also assayed in hamsters treated with estradiol implants for up to 7 months, a regimen known to induce kidney tumors. Significant increases in covalent oxidative modification to renal proteins over values in age-matched controls were detected after 1, 2, and 7 months of continuous estradiol exposure. It is concluded that the modification of the NaB3H4 reduction assay is a useful postlabeling method for monitoring free radical action in vivo. Furthermore, it is postulated that free radical damage in estrogen-treated hamster kidney plays a role in estrogen-induced carcinogenesis.
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PMID:Free radical-induced carbonyl content in protein of estrogen-treated hamsters assayed by sodium boro[3H]hydride reduction. 186 Aug 52


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