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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The hypothesis that low body iron stores are protective against cancer whereas high body stores promote tumor occurrence was examined in the 1-methyl-1-nitrosourea (MNU)-induced experimental model for breast cancer. Twenty-one-day-old female Sprague-Dawley rats were randomized into one of three experimental groups and fed a formulation of AIN-76A diet modified to be low in iron (2 p.p.m.), or the same diet supplemented with an adequate (120 p.p.m.) or excess (1200 p.p.m.) amount of iron provided as FeSO4.7H2O. Rats were maintained on their respective diets throughout the experiment which was terminated 32 weeks post carcinogen administration. Rats were injected i.p. with either 25 mg MNU/kg body wt or the saline-solvent in which MNU was dissolved at 50 days of age. In the first 14 weeks, dietary iron deficiency resulted in a low hematocrit and a decrease in weight gain. The appearance of mammary tumors was markedly suppressed in this group compared to those given an adequate or excess level of iron. It has been reported in the literature that reduction in weight gain due to food restriction at a period immediately after carcinogen administration severely inhibits the subsequent development of tumors. Thus the low tumor incidence in the iron-deficient rats during this time frame could be attributed to the combined effects of low hematocrit and depressed weight gain. For the period between week 14 and week 32, the hematocrit in the iron-deficient animals was maintained at a normal level, and the body wt of these rats was comparable to that of the controls given an adequate level of iron. The rate of tumor appearance in the iron-deficient group during the second half of the experiment was similar to that of the iron-adequate group in the first half of the experiment. In other words, it appeared that once hematocrit and body wt gain were restored to normal in the iron-deficient animals, tumor incidence was only minimally affected by low dietary iron. In the second half of the experiment, the tumor incidence in the adequate iron group seemed to have plateaued, whereas it continued to rise in the excess iron group. Thus excess iron appears to be more prominent than iron deficiency in modification of mammary carcinogenesis, especially when the confounding effects of low hematocrit and reduced weight gain are taken into consideration in the latter case.
Carcinogenesis 1991 Jan
PMID:Effect of dietary iron deficiency or excess on the induction of mammary carcinogenesis by 1-methyl-1-nitrosourea. 198 69

There are differences between young and adult organisms regarding toxokinetic aspects and clinical manifestations of heavy metal intoxications. Chronically, toxic Cd intake causes a microcytotic hypochromic anemia in young rats at lower exposure levels and after shorter exposure periods than in adult animals. Cd absorption is increased by co-administration of milk and in conjunction with iron deficiency. After long exposure periods toxic Cd concentrations accumulate in the kidney cortex; this process starts very early in life. In 3-year-old children Cd concentrations in the kidney can reach up to one-third of those found in adults. Hg++ and methyl-Hg can cause Hg encephalopathia, and frequently cause mental retardation in adults. Correspondingly, Hg++ accumulation in the brains of suckling rats is approx. 10 times higher than in grown animals. Milk increases the bioavailability of Hg++. In suckling rats Hg is bound to a greater extent to ligands in the erythrocytes. Methyl-Hg concentrations in breast milk reach 5% of those in maternal plasma and that is a severe hazard for breastfed children of exposed mothers. Toxic Pb concentrations can lead to Pb encephalopathia. A high percentage of surviving children have seizures and show signs of mental retardation. Anemia and reduced intelligence scores were recently observed in children after exposure to very low levels of Pb. Pb absorption is increased in children and after co-administration of milk. There are no definite proofs for carcinogenesis or mutagenesis after oral exposure to Cd, Hg, and Pb in man. Heavy metal concentrations were found in the same order of magnitude in commercial infant formulas and in breast milk. When infant formulas are reconstituted with contaminated tap water, however, Pb and Cd concentrations can be much higher. The average heavy metal uptake from such diets exceeds the provisional tolerable weekly intake levels set by the WHO for adults, calculated on the basis of an average food intake and a downscaled body weight. These considerations do not even provide for differences in absorption and distribution or for the increased sensitivity of children to heavy metal exposure. However, dilution effects for essential heavy metals were observed in fast-growing young children; this effect might be extrapolated to toxic metals. These theoretical considerations are compared with epidemiological evidence. A health statistic from Baltimore shows a decline of Pb intoxications in infants. This observation correlates with a simultaneous decline in exposure to Pb which was due, for example, to decreased use of lead dyes in house paints and the abolition of tin cans for infant food.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The toxicological estimation of the heavy metal content (Cd, Hg, Pb) in food for infants and small children]. 218

In order to further investigate the known influence of iron deficiency on 4NQO oral carcinogenesis in the rat, groups of iron-deficient and iron-sufficient Charles River white rats were painted with carcinogen for 8 weeks or 14 weeks and then left untreated for 32 weeks or 26 weeks respectively. Tumour development and epithelial dysplasia were assessed at the time of killing. Animals painted for 14 weeks showed more severe dysplasia than those painted for 8 weeks, but no significant differences were noted between corresponding iron-deficient and iron-sufficient groups.
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PMID:The effect of iron deficiency on early oral carcinogenesis in the rat. 309 92

The effect of iron deficiency on oral carcinogenesis was investigated in 30 young adult male Charles River white rats. In 15 animals, prior to the start of carcinogen treatment, iron deficiency anaemia was produced and subsequently maintained by a combination of low iron diet (12 mg Fe2+ kg-1 diet) and repeated venesection. Fifteen control animals were fed the same diet supplemented with iron to approximately 140 mg FE2+ kg-1 diet. All animals were treated with the carcinogen 0.5% 4-Nitroquinoline-N-oxide in propylene glycol which was painted on the palate 3 times weekly. Animals were killed when tumours were grossly evident. The mean haemoglobin levels at the start of carcinogen applications were 10.1 g dl-1 in the anaemic group and 14.1 g dl-1 in the control group, and at the time of killing were 8.2 g dl-1 in anaemic animals and 13.8 g dl-1 in controls. The incidence of animals developing squamous cell carcinomas was similar in both groups, but tumour development was significantly earlier in iron-deficient animals (mean 183 days) compared to controls (mean 229 days). Iron-deficient animals showed a significantly greater incidence of tongue tumours and control animals showed a significantly greater incidence of palatal tumours.
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PMID:The effect of iron deficiency on experimental oral carcinogenesis in the rat. 640 24

Male Fischer rats were maintained for a period of 17 weeks on an iron-deficient diet along with suitable controls. The effect of long term deprivation of iron on xenobiotic metabolism was studied by the activities of various drug metabolising enzymes in both liver as well as extra-hepatic tissues like lungs, kidneys and intestinal mucosa (I.M.). The results show that among the Phase I (activating) enzymes, the hepatic activities of benzo(a)pyrene hydroxylase (AHH) and microsomal epoxide hydrolase (mEH) are significantly reduced in iron deficiency. The other parameters of the activating system, namely cytochrome P450, aminopyrene demethylase (ADM) and aniline hydroxylase (AH), are not altered. Of the two Phase II (conjugating) enzymes studied, only uridine diphospho glucuronyl transferase (UDPGT) is found to be depressed, but not glutathione S-transferase (GST) in liver in iron deficiency. Activities of Phase I enzymes are markedly lowered in extra-hepatic tissues compared to liver; such depression is not observed in conjugating enzymes. Iron deficiency does not seem to make much impact on the enzyme activities of extra-hepatic tissues. Overall, the hepatic results suggest a defect in detoxification mechanisms in iron deficiency. Such impairment may very well predispose an iron-deficient host to an increased risk of carcinogenesis.
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PMID:Effect of long term iron deficiency on the activities of hepatic and extra-hepatic drug metabolising enzymes in Fischer rats. 785 40

The relationship between iron deficiency and carcinogenesis was studied using the carcinogen dimethylhydrazine to induce gastrointestinal tumors in Fischer 344 control and iron-deficient rats. Dimethylhydrazine (30 mg/body wt) was administered by gastric intubation 10 times over nine weeks. After 32 weeks, rats were sacrificed, and tumor incidence was assessed. The overall incidence of gastrointestinal tract tumors (colonic and duodenal) was higher in the iron-deficient (66%) than in the control group (46%). Whereas the incidence of colonic tumors was identical in control and iron-deficient groups, the duodenal tumor incidence was significantly elevated in iron deficiency. Five of 15 rats, i.e., 33.3%, in the iron-deficient group developed duodenal tumors; in the control group, only 1 of 15 rats developed a tumor (i.e., 6.6%). Also, iron-deficient rats had multiple tumors. Histological examination of the colon and duodenum revealed that the tumors were adenocarcinomatous in nature. Another notable feature in the iron-deficient group was the presence of atypical cells in the livers of carcinogen-treated iron-deficient rats. This study thus suggests that there is a greater incidence of tumors in iron deficiency and that the proximal part of the intestines seems to be the preferred site. The presence of atypical cells in the liver suggests that in iron deficiency, besides gastrointestinal tract tumors, the liver may also be a favored site for abnormalities.
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PMID:Effect of iron deficiency on DMH-induced gastrointestinal tract tumors and occurrence of hepatocyte abnormalities in Fischer rats. 787 98

Iron deficiency is an important nutritional problem in third world countries because it diminishes work performance. In meat-eating countries, iron excess may be more important than iron deficiency. Heme iron is more efficiently absorbed from the diet than inorganic iron, and iron excess can produce cellular oxidation in association with superoxide dismutase. Metal ion catalysis is linked to aging, coronary artery disease, stroke, carcinogenesis, neurodegenerative disorders, and inflammatory disorders. Prudence is advised in the excessive consumption of meat and iron supplementation of the diet until this process is more thoroughly investigated.
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PMID:Ironic catastrophes: one's food--another's poison. 819 51

Rats (Wistar, female, 4 weeks old) were fed iron-deficient (Fe-; 2.2 micrograms Fe/g) or manganese- and copper-deficient (Mn.Cu-; 0.3 microgram Mn/g, 0.4 microgram Cu/g) diets for 8 weeks to determine the oxidative damage of DNA by element deficiency. After feeding of the diets, 2-nitropropane (2-NP, 80 mg/kg body weight) was administered i.p. as an inducer of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) to the element-deficient rats. The hemoglobin concentration of rats in the Fe- group showed an induction of severe anemia (8.4 g/100 ml whole blood). In the Mn.Cu- group, Mn-superoxide dismutase (SOD) activities of plasma and Cu.Zn-SOD activities were significantly lower than that of the normal diet group. However, total SOD activities of plasma were not depressed severely in contrast to that of the liver in the Mn.Cu- group. Background (spontaneous) levels of 8-OH-dG in normal diet group were 0.96 +/- 0.37/10(5) deoxyguanosine (dG), however, significantly higher levels were detected in the Fe- group (1.56 +/- 0.19, P < 0.01). Conversely, a lower (but not significant) level of 8-OH-dG than the normal diet group were detected in the Mn.Cu- group (0.78 +/- 0.08). Six hours after 2-NP treatment, 8-OH-dG levels in liver DNA were significantly induced to 1.44 +/- 0.24 in the normal diet fed group 1.89 +/- 0.22 in the Fe- and 1.08 +/- 0.12 in the Mn.Cu- groups. Compared to the normal diet group, these induced levels of 8-OH-dG in the Fe- group were significantly higher (P < 0.05), and that in Mn.Cu- group were significantly lower (P < 0.05). The high level of 8-OH-dG in severe iron deficiency might be the results of: (i) an increase of hydroxyl radical generation by accumulated copper in hepatocytes; or (ii), a depression of enzymatic activity for removing 8-hydroxy-2'-deoxyguanosine in DNA, which is dependent on divalent cations. On the other hand, the low level of 8-OH-dG in manganese and copper deficiency might be the result of a decrease of lipid peroxidation which has been suggested to be an intermediator from active oxygen species to hydroxyl radical.
Carcinogenesis 1993 Feb
PMID:Spontaneous and 2-nitropropane induced levels of 8-hydroxy-2'-deoxyguanosine in liver DNA of rats fed iron-deficient or manganese- and copper-deficient diets. 838 15

Iron deficiency has been implicated in increasing the risk of GI tract cancers in humans. Among various mechanisms of carcinogenesis, oxidative damage to DNA is well known and, hence, the present experimental study was undertaken to investigate lipid peroxidation and activities of different antioxidant enzymes in iron deficiency to explain the higher risk of tumorigenesis. Two groups of male weanling Fischer rats maintained on iron sufficient (C) or iron deficient (D) diets for a period of 32 weeks were subdivided, from 3 weeks onwards, into two subgroups each. The carcinogen, dimethyl hydrazine was fed at a dose of 30 mg/kg/week IG for a period of 9 weeks to groups that were designated as (C+) and (D+). The other two subgroups (C-) and (D-) served as controls. After the experimental period, hepatic assays for lipid peroxidation (MDA production) and activities of various antioxidant enzymes were carried out. The results showed that MDA production was elevated by 50% and activity of superoxide dismutase significantly depressed in carcinogen-fed, iron-deficient group (D+) by 28% compared to deficient (D-) group. There was an increase in hepatic selenium-dependent glutathione peroxidase activity in iron-deficient and iron-deficient, carcinogen-treated groups to the extent of 57 and 59%, respectively, as compared to controls; however, induction of enzyme in response to carcinogen feeding, observed in the control group, was not evident in iron deficiency. Liver catalase was not altered between control and deficient groups. These results suggest that prolonged iron deficiency superimposed with carcinogen ingestion may render the host susceptible to a greater risk of tumorigenesis through oxidative stress.
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PMID:Lipid peroxidation and activities of antioxidant enzymes in iron deficiency and effect of carcinogen feeding. 879 Oct 98


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