Anaemia among school children of different socioeconomical status in a city of Southern Brazil.

Background: Iron deficiency is one of the leading causes of anaemia, with those most affected being children and women of childbearing age, in Brazil there is a scarcity of studies involving the local prevalence of anaemia. Aim: To evaluate anaemia and associated factors in schoolchildren in Santa Cruz do Sul through the analysis of biochemical and haematological markers and parasitological examination of faeces. Subjects and methods: School children from 10 to 12 years of age were evaluated through complete blood count, serum ferritin, C-reactive protein and stool parasitological examination, as well as socio-demographic characteristics and prophylaxis with ferrous sulphate in childhood. Results: It was found that 13.0% of the population was anaemic, girls were very slightly overrepresented among the anaemic children. Only 5.3% had altered haematocrit levels; 26.6% had low Mean Corpuscular Volume levels; 18.4% had low ferritin levels; 2.4% had increased C-reactive protein levels, and 21.7% had altered eosinophils. As for the socioeconomic level, classes A2 and D presented lower haemoglobin levels, as well as class D presenting lower ferritin levels, although without statistical significance. Only 6.0% of the population presented iron-deficiency anaemia and 46.0% of the schoolchildren had used ferrous sulphate supplementation in childhood. Conclusion: The prevalence of anaemia in the studied municipality is low, probably due to the high municipal human development index. Epidemiological studies are essential to characterise the population in a systematic form, to prevent future problems.

Iron supplementation does not aggravate impaired glucose tolerance and sugar overload-induced genotoxicity in rats.

High sugar intake is a major risk factor for metabolic disorders. Genotoxicity is an important factor in diabetes onset, and iron (Fe) may be an aggravating element. However, this relationship is still poorly established. Thus, this study evaluated whether Fe supplementation could aggravate obesity, impaired glucose tolerance, and sugar overload-induced genotoxicity in rats. A total of 24 rats were treated with different diets: standard diet (SD, n = 8), invert sugar overload (320 g/L, HSD, n = 8), or Fe plus invert sugar overload (2.56 mg/L of Fe2+, Fe-HSD, n = 8) for four months. After treatment, the Fe-HSD group showed no excessive weight gain or impaired glucose tolerance. DNA damage in blood, as assessed by comet assay, gradually increased in HSD during treatment (p < 0.001), whereas Fe-HSD showed a nonlinear increase in DNA damage. Moreover, Fe-HSD presented 0.6-fold more DNA damage compared with SD (p = 0.0055) in the 1st month of treatment. At months 2 and 3, results show a ≥ 1.4-fold increase in HSD and Fe-HSD DNA damage, respectively, compared with SD (p < 0.01). At the end of the experiment, only HSD DNA damage differed from SD (1.5-fold more, p = 0.0196). Fe supplementation did not aggravate the invert sugar-induced DNA damage (p > 0.05). In the pancreas, results showed no differences in DNA damage. Mutagenicity, evaluated by micronucleus testing, was not observed regardless of treatment (p = 0.428). Fe supplementation, in the evaluated concentration, did not aggravate weight gain, impaired glucose tolerance, and sugar overload-induced genotoxicity in rats.

Invert sugar induces glucose intolerance but does not cause injury to the pancreas nor permanent DNA damage in rats.

The high consumption of sugars is linked to the intermediate hyperglycemia and impaired glucose tolerance associated with obesity, inducing the prediabetes. However, the consequences of excessive invert sugar intake on glucose metabolism and genomic stability were poorly studied. The aim of this study was to evaluate the effects of invert sugar overload (32%) in rats, analyzing changes in obesity, glucose tolerance, pancreatic/hepatic histology and primary and permanent DNA damage. After 17 weeks, the rats became obese and had an excessive abdominal fat, as well as presented impaired glucose tolerance, caused by higher sugar caloric intake. Primary DNA damage, evaluated by the comet assay, was increased in the blood, however not in the pancreas. No protein carbonylation was seen in serum. Moreover, no increase in permanent DNA damage was seen in the bone marrow, evaluated using the micronucleus test. Some rats presented liver steatosis and that the pancreatic islets were enlarged, but not significantly. In this study, invert sugar altered the glucose metabolism and induced primary DNA damage in blood, but did not cause significant damage to the pancreas or liver, and neither changes in the levels of oxidative stress or permanent DNA damage.

Influence of hesperidin and vitamin C on glycemic parameters, lipid profile, and DNA damage in rats treated with sucrose overload.

We evaluated the influence of hesperidin and vitamin C (VitC) on glycemic parameters, lipid profile, and DNA damage in male Wistar rats treated with sucrose overload. Rats were divided into six experimental groups: I-water control; II-sucrose control; III-hesperidin control; IV-VitC control; V-co-treatment of sucrose plus hesperidin; VI-co-treatment of sucrose plus VitC. We measured the levels of triglycerides, total cholesterol, HDL-c, LDL-c, fasting glucose, and glycated hemoglobin (A1C). DNA damage was evaluated in blood and brain cells using the comet assay and the micronucleus test was used to evaluate chromosomal damages in the rat bone marrow. Co-treatment with VitC, but not with hesperidin, normalized the serum glucose. No effect of co-treatments was observed on A1C. The co-treatment with VitC or hesperidin did not influence the lipid profile (p>0.05). Rats co-treated with hesperidin had a significantly lower DNA damage level in blood (p<0.05) and brain (p<0.05). Rats treated with VitC only, but not those co-treated with VitC plus sucrose, had significantly higher DNA damage in brain (p<0.05). No significant differences were observed in the results of micronucleus test (p>0.05). Hesperidin and VitC showed different effects on sucrose and DNA damage levels. While VitC lowered the serum glucose, hesperidin reduced the DNA damage.

High consumption of sucrose induces DNA damage in male Wistar rats.

The purpose of this study was to determine the effects of the high consumption of sucrose on the levels of DNA damage in blood, hippocampus and bone marrow of rats. Male Wistar rats were treated for 4 months with sucrose (10% for 60 initial days and 34% for the following 60 days) in drinking water, and then, glycemia and glycated hemoglobin (A1C) were measured. Levels of DNA damage in blood and hippocampus were evaluated by the comet assay. The micronucleus test was used to evaluate chromosomal damages in the bone marrow. The sucrose treatment significantly increased (p<0.01) the serum glucose levels (~20%) and A1C (~60%). The level of primary DNA damage was significantly increased (p<0.05) in hippocampal cells (~60%) but not in peripheral blood leukocytes (p>0.05). Additionally, it was observed a significative increase (p<0.05) in the markers of chromosomal breaks/losses in bone marrow, as indicated by the micronucleus test. This is the first study that evaluated DNA damage induced by high sucrose concentration in the hippocampus and bone marrow of rats. Sucrose-induced DNA damage was observed in both tissues. However, the mechanism of sucrose toxicity on DNA remains unknown.

FTO polymorphism, cardiorespiratory fitness, and obesity in Brazilian youth.

OBJECTIVES: The aim of the present study was to evaluate the relationship between the rs9939609 fat mass and obesity-associated (FTO) polymorphism and cardiorespiratory fitness (CRF) with overweight/obesity outcomes in youth. METHODS: This study included 420 youths, comprising 211 boys and 209 girls aged 7-17. Overweight/obesity were evaluated by body mass index (BMI), waist circumference (WC), and the percentage of fat (PF) according to two skinfold thickness measurements. Genotyping of the rs9939609 polymorphism was conducted using real-time Polymerase Chain Reaction (PCR) utilizing TaqMan(®) probes, and CRF was evaluated through a 9-minute run/walk test, categorized as fit or unfit. Logistic regression was utilized to evaluate a possible association between the polymorphism and CRF, with three obesity indicators evaluated. RESULTS: Individuals with the genotype risk (AA) of FTO polymorphism rs9939609 showed higher prevalence of overweight/obesity, as evaluated by BMI (OR: 3.21; CI: 1.71-6.05), WC (OR: 2.59; CI: 1.35-4.97), and PF (OR: 2.59; CI: 1.36-4.92). Additionally, students with the AA genotype in the unfit model had a significant odds ratio for obesity (OR: 4.40; CI: 1.83-10.61 for BMI; OR: 3.54; CI: 1.58-7.96 for WC), whereas we did not observe associations between the AA genotype with BMI and WC using the fit model. Conversely, PF was associated with the AA genotype only in the fit model (OR: 3.24; CI: 1.26-8.34). CONCLUSIONS: This study demonstrated that the rs9939609 (FTO) polymorphism showed a relationship with obesity in the population studied and an interaction with CRF. Students with low levels of CRF and the AA genotype have a higher risk of being overweight/obese. This association was not found in students with higher levels of CRF. Am. J. Hum. Biol. 28:381-386, 2016. © 2015 Wiley Periodicals, Inc.

DNA damage and cytotoxicity in pathology laboratory technicians exposed to organic solvents.

The aim of this study was to evaluate potential DNA damage and cytotoxicity in pathology laboratory technicians exposed to organic solvents, mainly xylene. Peripheral blood and buccal cells samples were collected from 18 technicians occupationally exposed to organic solvents and 11 non-exposed individuals. The technicians were sampled at two moments: Monday and Friday. DNA damage and cytotoxicity were evaluated using the Comet Assay and the Buccal Micronucleus Cytome assay. Fifteen subjects (83.5%) of the exposed group to solvents complained about some symptom probably related to contact with vapours of organic solvents. DNA damage in the exposed group to solvents was nearly 2-fold higher on Friday than on Monday, and in both moments the individuals of this group showed higher levels of DNA damage in relation to controls. No statistical difference was detected in buccal cell micronucleus frequency between the laboratory technicians and the control group. However, in the analysis performed on Friday, technicians presented higher frequency (about 3-fold) of karyolytic and apoptotic-like cells (karyorrhectic and pyknotic) in relation to control group. Considering the damage frequency and the working time, a positive correlation was found in the exposed group to solvents (r=0.468; p=0.05). The results suggest that pathology laboratory workers inappropriately exposed to organic solvents have increased levels of DNA damage.

Biological functions of selenium and its potential influence on Parkinson's disease.

Parkinson's disease is characterized by the death of dopaminergic neurons, mainly in the substantia nigra, and causes serious locomotor dysfunctions. It is likely that the oxidative damage to cellular biomolecules is among the leading causes of neurodegeneration that occurs in the disease. Selenium is an essential mineral for proper functioning of the brain, and mainly due to its antioxidant activity, it is possible to exert a special role in the prevention and in the nutritional management of Parkinson's disease. Currently, few researchers have investigated the effects of selenium on Parkinson´s disease. However, it is known that very high or very low body levels of selenium can (possibly) contribute to the pathogenesis of Parkinson's disease, because this imbalance results in increased levels of oxidative stress. Therefore, the aim of this work is to review and discuss studies that have addressed these topics and to finally associate the information obtained from them so that these data and associations serve as input to new research.

Recognition memory and DNA damage in undernourished young rats.

This study evaluated the recognition memory and the levels of DNA damage (blood and hippocampus) in undernourished young Wistar rats. The experiment was conducted along 14-week with rodents divided in control group (CG, n=8) and undernourished group (UG, n=12) which was submitted to caloric restriction. Nutritional status for undernutrition was defined by Body Mass Index (BMI) ≤0.45g/cm2 and by weighting the organs/tissue (liver, spleen, intestine, peritoneal fat, kidney and encephalon). The Novel Object Recognition Test assessed recognition memory and the Comet Assay evaluated the levels of DNA damage. Student t test, 2-way ANOVA and Pearson's correlation analysis were used and the significance level was of p<0.05. The UG showed lower BMI and organ/tissue weights than CG (p<0.001). In short-term memory, the recognition rate was higher in the UG (p<0.05), only after 4 weeks. In the long-term memory, again recognition rate was higher in the UG than the CG, after 4 weeks (p<0.001) and 14 weeks (p<0.01). The UG showed decreased levels of DNA damage in the blood (p<0.01) and increased levels in the hippocampus (p<0.01). We concluded in this study that the undernutrition by caloric restriction did not cause impairment in recognition memory, however induced DNA damage in the hippocampus.

Ischemic versus pharmacologic hepatic preconditioning.

BACKGROUND: Hepatic ischemia-reperfusion injury has a significant impact on liver resection and transplantation. Many strategies have been developed to reduce the effects of ischemia-reperfusion injury, including pharmacologic and ischemic preconditioning; however, studies comparing these two methods are lacking. MATERIAL AND METHODS: An experimental study was performed in a swine model. Eighteen swine were randomly assigned to three different groups: an ischemic preconditioning (IschPC) group, a pharmacologic preconditioning (PharmPC) group, and a control group. All animals underwent a 40-min liver ischemia, followed by 40 min of reperfusion. The IschPC group received a short period of ischemia (10 min) and a short period of reperfusion (15 min) before prolonged ischemia. The PharmPC group received inhaled sevoflurane for 30 min before prolonged ischemia. The control group did not receive any intervention before prolonged ischemia. Blood samples and liver tissue were obtained after ischemic and reperfusion periods. Injury was evaluated by measure of DNA damage (using COMET assay) and serum biochemical markers (transaminases, alkaline phosphatase, amylase, bilirubin, and C-reactive protein [CRP]). RESULTS: No significant difference was found in serum biochemical markers, except for the C-reactive protein level that was lower in the PharmPC group than in the control group soon after hepatic ischemia. Soon after prolonged ischemia, DNA damage index, both in blood samples and in liver tissue samples, was similar among the groups. However, an increase in DNA damage after reperfusion was higher in the control group than in the PharmPC group (P < 0.05). The increase in DNA damage in the IschPC group was half of that observed in the control, but this difference was not statistically significant. CONCLUSIONS: Our results suggest an early protective effect of PharmPC (lower levels of C-reactive protein soon after ischemia). The protective effect observed after reperfusion was higher with PharmPC than with ischemic preconditioning. The simultaneous use of both methods could potentiate protection for ischemia-reperfusion.

Water quality of urban streams: the Allium cepa seeds/seedlings test as a tool for surface water monitoring.

The present study investigates the genotoxic, mutagenic, and cytotoxic potential of surface waters in urban streams using Allium cepa and analyzes the applicability of this assay for environmental monitoring. Water samples were collected from three streams located in the urban area of a municipality in the south of Brazil. For each stream, two samples were collected, one upstream and one downstream of the pollution discharge site. Physicochemical evaluation indicated that all samples had various degrees of environmental impact, but substantial impact was seen for the downstream samples of the Preto and Pedras streams. All samples increased the frequency of chromosome aberrations (P < 0.05). The sample from Pedras downstream site also caused a decrease in mitotic index (P < 0.08) and increase in micronuclei (P < 0.08) frequency, indicating potential cytotoxicity and mutagenicity. The Pedras stream receives mixed industrial and urban wastewater, while the Lajeado and Preto streams receive wastewater predominantly domestic in nature, which may partially explain the difference in toxicity among the samples. Moreover, the Allium cepa seeds/seedlings were shown to be extremely sensitive in detecting the genotoxicity of environmental water samples and can be applied as the first tool for environmental health hazard identification and prediction.

Orange juice and cancer chemoprevention.

Orange juice (OJ) is among the most consumed fruit juices worldwide, and its chemopreventive action is fairly addressed in the literature. This review critically presents the available evidence linking OJ with cancer chemoprevention and on discussing the putative mechanisms and negative health effects. The chemopreventive action of OJ is related to its effect on metabolic enzymes and its antiinflammatory, cytoprotective/apoptotic, hormonal, cell signaling-modulating, antioxidant, and antigenotoxic effects. Most studies on OJ are in vitro, and few are conducted in vivo. Results from in vitro studies must be interpreted carefully because these findings do not consider in vivo bioavailability. However, such results are useful for studying the impact of different processing and storage methods on OJ's chemopreventive effect. Evidence of OJ's chemoprevention in humans is limited. OJ is antimutagenic in bacteria and antigenotoxic in humans and rodents. Studies using rodent cancer models showed that OJ is cancer chemopreventive, influencing either the induction stage or the promotion stage. The composition and, therefore, the chemopreventive action of OJ might be influenced by different cultivars, climates, extraction methods, packaging, storage temperatures, and shelf lives, among other factors. Epidemiological studies and randomized controlled intervention studies in humans evaluating the chemopreventive effect of OJ, taking into consideration variability in OJ composition, are needed.

DNA damage and cytotoxicity in adult subjects with prediabetes.

Prediabetes (intermediate hyperglycemia) is a high-risk state for diabetes that is defined by higher than normal glycemic levels that are below the level required for a diagnosis of diabetes. Prediabetes is characterized by oxidative stress, yet the associated DNA damage and cytotoxicity remain unknown to date. Therefore, we evaluated the relationship between glycemic alterations, DNA damage and cytotoxicity in the lymphocytes of individuals with pre-diabetes. Fasting plasma glucose (FPG) and glycated hemoglobin (A1C) levels were quantified and used as inclusion criteria. Anthropometric parameters were also evaluated. The cytokinesis-block micronucleus cytome assay (CBMN Cyt) was used to evaluate DNA damage and cytotoxicity. FPG correlated with A1C (r=0.562, p=0.002). Because A1C is the best predictor of diabetes complications, the association between A1C and the evaluated variables was assessed. The waist-hip ratio correlated with A1C (p<0.01). Regarding DNA damage, the frequency of nucleoplasmic bridges correlated with A1C (p<0.05). Both apoptosis and necrosis correlated with A1C (p<0.05). The overall frequency of DNA damage and cytotoxicity also correlated with A1C (p<0.01). Additional studies evaluating cell cycle and cell death patterns in prediabetes are necessary.

Rapid and low-cost liquid biopsy with ATR-FTIR spectroscopy to discriminate the molecular subtypes of breast cancer.

Breast cancer (BC) is the most prevalent cancer worldwide. The prognosis and survival of these patients are directly related to the diagnostic stage. Even so, the gold standard screening method (mammography) has a long waiting period, high rates of false positives, anxiety for patients, and consequently delays the diagnosis by core needle biopsy (invasive method). Alternatively, the Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy is a noninvasive, low-cost, rapid, and reagent-free technique that generates the spectral metabolomic profile of biomolecules. This makes it possible to assess systemic repercussions, such as the BC carcinogenesis process. Blood plasma samples (n = 56 BC and n = 18 controls) were analyzed in the spectrophotometer in the ATR-FTIR mode. For the exploratory analysis of the data, interval Principal Component Analysis (iPCA) was used, and for predictive chemometric modeling, the Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) algorithm with validation by leave-one-out cross-validation. iPCA in the region of 1118-1052 cm-1 (predominantly DNA/RNA bands) showed significant clustering of molecular subtypes and control. The OPLS-DA model achieved 100% accuracy with only 1 latent variable and Root Mean Square Error of Cross-Validation (RMSECV) < 0.005 for all molecular subtypes and control. The wavenumbers (cm-1) with the highest iPCA peaks (loadings: 1117, 1089, 1081, 1075, 1057, and 1052) were used as input to MANOVA (Wilks' Lambda, p < 0.001 between molecular subtypes and control). The rapid and low-cost detection of BC molecular subtypes by ATR-FTIR spectroscopy would plausibly allow initial screening and clinical management, improving prognosis, reducing mortality and costs for the health system.

Iron and genome stability: an update.

Iron is an essential micronutrient which is required in a relatively narrow range for maintaining metabolic homeostasis and genome stability. Iron participates in oxygen transport and mitochondrial respiration as well as in antioxidant and nucleic acid metabolism. Iron deficiency impairs these biological pathways, leading to oxidative stress and possibly carcinogenesis. Iron overload has been linked to genome instability as well as to cancer risk increase, as seen in hereditary hemochromatosis. Iron is an extremely reactive transition metal that can interact with hydrogen peroxide to generate hydroxyl radicals that form the 8-hydroxy-guanine adduct, cause point mutations as well as DNA single and double strand breaks. Iron overload also induces DNA hypermethylation and can reduce telomere length. The current Recommended Dietary Allowances (RDA) for iron, according with Institute of Medicine Dietary Reference Intake (DRI), is based in the concept of preventing anemia, and ranges from 7mg/day to 18mg/day depending on life stage and gender. Pregnant women need 27mg/day. The maximum safety level for iron intake, the Upper Level (UL), is 40-45mg/day, based on the prevention of gastrointestinal distress associated to high iron intakes. Preliminary evidence indicates that 20mg/day iron, an intake slightly higher than the RDA, may reduce the risk of gastrointestinal cancer in the elderly as well as increasing genome stability in lymphocytes of children and adolescents. Current dietary recommendations do not consider the concept of genome stability which is of concern because damage to the genome has been linked to the origin and progression of many diseases and is the most fundamental pathology. Given the importance of iron for homeostasis and its potential influence over genome stability and cancer it is recommended to conduct further studies that conclusively define these relationships.

DNA damage in children and adolescents with cardiovascular disease risk factors.

The risk of developing cardiovascular disease (CVD) is related to lifestyle (e.g. diet, physical activity and smoking) as well as to genetic factors. This study aimed at evaluating the association between CVD risk factors and DNA damage levels in children and adolescents. Anthropometry, diet and serum CVD risk factors were evaluated by standard procedures. DNA damage levels were accessed by the comet assay (Single cell gel electrophoresis; SCGE) and cytokinesis-blocked micronucleus (CBMN) assays in leukocytes. A total of 34 children and adolescents selected from a population sample were divided into three groups according to their level of CVD risk. Moderate and high CVD risk subjects showed significantly higher body fat and serum CVD risk markers than low risk subjects (P<0.05). High risk subjects also showed a significant increase in DNA damage, which was higher than that provided by low and moderate risk subjects according to SCGE, but not according to the CBMN assay. Vitamin C intake was inversely correlated with DNA damage by SCGE, and micronucleus (MN) was inversely correlated with folate intake. The present results indicate an increase in DNA damage that may be a consequence of oxidative stress in young individuals with risk factors for CVD, indicating that the DNA damage level can aid in evaluating the risk of CVD.

Potential Ameliorative Effects of Chromium Supplementation on Glucose Metabolism, Obesity, and Genomic Stability in Prediabetic Rat Model.

Chromium (III) (Cr(III)) effect on improving glucose, body mass loss, and genomic stability has been extensively studied in models of type 2 diabetes. However, there is a lack of studies evaluating its effect on prediabetes. Thus, this study evaluates the effects of Cr(III) as dietetic supplementation on glucose metabolism, obesity, and genomic stability on prediabetic rat model using high-invert sugar. Male Wistar rats were divided randomly into four treatment groups: (1) control, receiving standard diet (control); (2) prediabetic (PD), receiving a 32% of invert sugar; (3) Cr(III), receiving chromium (III) chloride (CrCl3•6H2O) (58.4 mg/L); and (4) Cr(III) + PD, receiving CrCl3•6H2O in combination with high-invert sugar. Cr(III) supplementation significantly reduced blood glucose (123.00 ± 8.29 mg/dL vs. 115.30 ± 9.31 mg/dL, p = 0.015) and partially reduced area under the 120-min blood glucose response curve (AUC) in PD rats (p = 0.227). Moreover, Cr(III) attenuated weight gain (187.29 ± 38.56 g vs. 167.22 ± 29.30 g, p = 0.004), significantly reducing body mass index (0.68 ± 0.04 g/cm2 vs. 0.63 ± 0.04 g/cm2, p < 0.001), Lee index (0.30 ± 0.01 vs. 0.28 ± 0.01, p < 0.001), and peritoneal fat (p < 0.001). Regarding genomic stability, high-invert sugar, Cr(III), or the combination of both did not produce changes in oxidative stress, DNA damage in pancreas, or cytotoxicity markers. These data suggest that Cr(III) supplementation improved partially glucose metabolism and reduced obesity in rat model PD due to high-invert sugar without influence in genomic stability.

Macro and micro minerals: are frozen fruits a good source?

Fruits are rich in minerals, which are essential for a wide variety of metabolic and physiologic processes in the human body. The use of frozen fruits has greatly spread in the last years not only in the preparation of juices, but also as raw material for yogurts, candies, cookies, cakes, ice creams, and children's food. However, up to now there is no data about the mineral profile of frozen fruits. This is the first database to quantify the levels of minerals in 23 samples of frozen fruits, including the most used around the world and some native fruits from the Amazon rainforest in Brazil. Considering the Dietary Reference Intakes, 100g of frozen fruits can provide 0.2 to 2.8% of macro and 2.5 to 100% of microminerals for adults (31-50 years old). Although geographical differences should be considered, these data can help to plan diets and to develop population interventions aiming to prevent chronic diseases.

A possible link between iron deficiency and gastrointestinal carcinogenesis.

There is definitive evidence that iron overload induces oxidative stress and DNA damage, which can enhance carcinogenic risk. However, other evidence suggests that iron deficiency and anemia also increase oxidative stress and DNA damage, which might increase carcinogenesis risk, especially in the gastrointestinal (GI) tract. The aim of this review is to provide essential background information for the accurate interpretation of future research on iron deficiency and increased GI cancer risk. Based on clinical, epidemiological, and experimental evidence, we discuss how iron deficiency might contribute to increased cancer risk through the impairment of several iron-dependent metabolic functions that are related to genome protection and maintenance (e.g., immune responses against cancer-initiated cells, metabolism of toxic compounds, and redox regulation of DNA biosynthesis and repair). Some epidemiological studies have indicated increased risk of GI tumors among individuals with low iron intake or low somatic iron stores, and in vivo data from rodent cancer models indicates the early progression of GI tumors during iron deficiency. Given the preliminary but consistent evidence relating iron deficiency to cancer risk and the fact that iron deficiency affects about one third of the world's population, further studies are needed to define the extent to which iron deficiency might increase GI cancer risk.

Length of treatment and dose as determinants of mutagenicity in sickle cell disease patients treated with hydroxyurea.

Hydroxyurea (HU) is an antineoplastic drug widely used in the clinical management of patients with sickle cell disease (SCD), and many questions related with its use remain unresolved. Given the severity of SCD, HU benefits, although not thoroughly confirmed, seem to outweigh its potential carcinogenicity. This study aimed to assess the genotoxicity associated with HU dose and treatment length by evaluating mutagenicity in patients with SCD treated with HU (SCHU) using the cytokinesis-block micronucleus assay (CBMN) in white cells. The study was conducted with 35 individuals in the SCHU group and 34 controls matched according to age, sex and smoking habit. CBMN results showed an increase (p=0.032) in the number of micronuclei (MN), but not of nucleoplasmic bridges (NPB) or nuclear buds (NBUD) in the SCHU group. The increased frequency of MN in the SCHU group was significantly correlated with treatment length and final HU dose, which confirms that patients with SCD treated with HU should be carefully monitored to reduce the risk of carcinogenicity.