DNA Damage In Blood Cells Research Articles

Genotoxic effect of selenium arabinogalactan nanocomposite on nucleated blood cells

Introduction. Selenium (Se) nanoparticles have attracted the interest of researchers for various applications due to their unusual properties. Despite their advantages, Se nanoparticles also have toxic effects, so for their successful use it is necessary to know the doses that are safe for the use. An important component in the development of pathological processes is the occurrence of DNA damage after exposure to Se nanoparticles, which can lead to severe disorders. Materials and methods. Male white rats were orally administered a solution of Se nanocomposite at a dose of 500 μg/kg for 10 days. The genotoxicity of the nanocomposite under study was assessed by the occurrence of DNA damage in blood cells using the DNA comet method in the alkaline version. The results were obtained during 2 stages: one day after exposure and after 4 months to identify the persistence or absence of a negative effect. Results. With using the DNA comet method, intragastric administration of Se nanocomposite was found to cause the damage to the DNA structure, and this effect persists not only 24 hours after exposure, but also 4 months later. Limitations. The study is limited to the study of DNA fragmentation on the next day after a 10-day exposure to Se nanocomposite in male white rats and during the long-term period after 4 months. Conclusion. The study revealed persistent DNA damage in the nucleated blood cells of male albino rats, which apparently may be associated with the main mechanism of Se toxicity: nonspecific replacement of sulfur in sulfur-containing amino acids. However, the toxic effects of the nanocomposite may also be caused by its pro-oxidant properties, which requires further confirmation.

DNA fragmentation as a bioindicator of peat fires’ smoke exposure

Introduction. The impact of combustion products of organic substances on the body is known to be accompanied by the accumulation of DNA damage, which can lead to mutations and pathological changes in the cell and the whole organism. The prevalence and scale of this phenomenon poses an important task for studying the consequences that occur in smoke-exposed organisms and their offspring. 
 Materials and methods. The conditions of real peat smoke were reproduced for 40 minutes with a CO concentration of 99±2.5 mg/m3 with using of experimental bio modelling. The genotoxicity of peat fire smoke after exposure to male white rats was assessed by the occurrence of DNA damage in blood cells using the DNA comet method in the alkaline version. In the first part of the experiment, males were directly exposed to the smoke of a peat fire; in the second part – their sexually mature offspring of both sexes were examined for the occurrence of DNA damage in blood cells.
 Results. The males of the parental generation and offspring were found to be resistant to the effects of smoke components, which was confirmed by the absence of statistical significance in terms of «% DNA in the comet tail» compared with the control. At the same time, females of the received generation showed a statistically significant increase in blood cell DNA damage compared to the control group. 
 Limitations. The study was limited to the study of DNA fragmentation after a single 40-minute exposure to peat smoke in male white rats and their intact offspring. 
 Conclusion. The data obtained in this investigation indicate that damage to the DNA structure in the offspring of male rats exposed to peat smoke containing CO at a concentration of 99±2.5 mg/m3 can be considered as a bioindicator of genotoxic effects induced in the next generation.

Measuring blood cell DNA damage using the PIG-A mutation and CBMN assay in pancreatic cancer patients: a pilot study.

Pancreatic cancer still has one of the worst prognoses of all solid malignancies, despite developments in cancer knowledge and care. Research into pancreatic cancer has not fully translated into clinical improvements and as a result, fewer than 1% of patients survive 10 years post-diagnosis. This bleak outlook for patients could be improved by earlier diagnosis. The human erythrocyte phosphatidylinositol glycan class A (PIG-A) assay monitors the mutation status of the X-linked PIG-A gene by measuring glycosyl phosphatidylinositol (GPI)-anchored proteins on the extracellular surface. We have previously identified an elevated PIG-A mutant frequency in oesophageal adenocarcinoma patients and here investigate whether this could be seen in a pancreatic cancer cohort, given the urgent need for novel pancreatic cancer biomarkers. In our pilot study, an elevated PIG-A mutant frequency (5.775 × 10-6 (95% CI 4.777-10) mutants per million) was seen in pancreatic cancer patients (n = 30) when compared to the non-cancer control group (n = 14) who had an erythrocyte mutant frequency of 4.211 × 10-6 (95% CI 1.39-5.16) mutants per million (p = 0.0052). A cut-off value of 4.7 mutants per million provided an AUROC of 0.7595 with a sensitivity of 70% and specificity of 78.57%. A secondary measure of DNA damage in an alternative blood cell population also showed an increase in peripheral lymphocytes using the cytokinesis-block micronucleus assay (p = 0.0164) (AUROC = 0.77, sensitivity = 72.22%, specificity = 72.73%). The micronucleus frequency and PIG-A status show some potential as blood-based biomarkers of pancreatic cancer, but further investigations of these DNA damage tests are required to assess their utility in pancreatic cancer diagnosis.

Expression variation of OGG1 and HPRT gene and DNA damage in arsenic exposed industrial workers.

Arsenic exposure alters redox balance, induces DNA damage, and deregulates many genes. OGG1 gene involved in base repair mechanism, for excision of 8-oxoguanine (8-oxoG) from DNA formed as a result of accumulation of ROS in cell. HPRT gene encode transferase enzymes involved in purine recycling mechanism. The main focus of the study was to evaluate the expression variation in HPRT, OGG1 gene expression, and DNA damage of industrial workers. Blood samples of 300 occupational workers were collected from welding, brick kiln, furniture, pesticide, and paint industry (n = 60/industry) to evaluate the expression variation in HPRT, OGG1 gene expression, and DNA damage in blood cells by comet assay along with age and gender matched 300 control individuals. Blood arsenic content was higher (P<0.001) in an industrial group compared to the control. OGG1 and HPRT expression were (P<0.05) downregulated in exposed workers compared to controls. Spearman correlation analysis showed a significant positive correlation between HPRT vs OGG1 (P< 0.0001) in exposed workers compared to controls. Altered expression of both genes was observed between workers with <25years and >25years of age as well as between workers with <10years and >10year exposure. Reduced expression (P<0.05) of both genes and a high extent of DNA damage was evident in exposed smokers compared to respective non-smokers. DNA fragmentation was higher (P<0.05) in the furniture, welding and brick kiln group compared to control, and other industries. The present study suggests that altered expression of OGG1 and HPRT gene induce oxidative stress, showed a negative impact on the recycling of purines leading to DNA damage which increase the vulnerability of workers to carcinogenicity.

Background DNA damage is higher in summer than winter in both free-living and captive birds.

Although stress can cause overall damage to the genome, it is currently unknown whether normal background damage to DNA varies throughout the annual cycle. If DNA damage did vary seasonally, it would have major implications on environmental-genomic interactions. We measured background DNA double-stranded breaks using the neutral comet assay in fivetissues (nucleated red blood cells, abdominal fat, hippocampus, hypothalamus, and liver) in fourcohorts of house sparrows (Passer domesticus): free-living summer, captives on a summer light cycle, free-living winter, and captives on a winter light cycle. The experiment was designed to answer threequestions: (1) Is red blood cell DNA damage representative of other tissues? (2) Is DNA damage in captive birds representative of DNA damage in free-living birds? (3) Does DNA damage show seasonality? We found that (1) blood is a representative tissue, (2) captive animals are representative of free-living animals, and (3) DNA damage is higher in the summer than in the winter. These data indicate that red blood cells can be an index of DNA damage throughout the body and that background levels of DNA damage show substantial seasonal variation. The latter result suggests the possibility that underlying molecular mechanisms of DNA damage and/or repair also change seasonally.

Cardiac arrhythmia catheter ablation procedures guided by x-ray imaging: N-acetylcysteine protection against radiation-induced cellular damage (CARAPACE study): study design.

Catheter ablation (CA) procedures are characterized by exposure to ionizing radiations (IR). IR can cause DNA damage and may lead to carcinogenesis if not efficiently repaired. The primary endpoint of this study is to investigate whether intravenous administration of N-acetylcysteine prior to CA procedure may prevent systemic oxidative stress and genomic DNA damage induced by exposure to IR. The "Cardiac Arrhythmia catheter ablation procedures guided by x-Ray imaging: N-Acetylcysteine Protection Against radiation induced Cellular damagE" (CARAPACE) study is a prospective, randomized, single-blinded, parallel-arm monocenter study enrolling 550 consecutive patients undergoing CA at the Arrhythmology Unit of Centro Cardiologico Monzino (CCM). Inclusion criteria are age ≥ 18, indication for CA procedure guided by IR imaging, and written informed consent. IR levels will be measured via fluoroscopy time, effective dose, and dose area product. Glutathione and glutathione disulfide concentrations will be measured, and urinary levels of 8-iso-prostaglandin-F2α and 8-hydroxy-2-deoxyguanosine will be quantified. The enrolled patients will be randomized 1:1 to the N-acetylcysteine group or to the control group. We expect that pre-operative administration of N-acetylcysteine will prevent IR-induced systemic oxidative stress. The study will provide data on oxidative DNA damage assessed by urinary 8-hydroxy-2-deoxyguanosine levels and direct evidence of genomic DNA damage in blood cells by comet assay. Catheter ablation procedures can lead to IR exposure and subsequent DNA damage. N-acetylcysteine administration prior to the procedure may prevent them and therefore lead to less possible complications. www.clinicaltrials.gov (NCT04154982).

The genotoxicity of an organic solvent mixture: A human biomonitoring study and translation of a real-scenario exposure to in vitro

This study aimed to evaluate occupational exposure to a styrene and xylene mixture through environmental exposure assessment and identify the potential genotoxic effects through biological monitoring. Secondly, we also exposed human peripheral blood cells in vitro to both xylene and styrene either alone or in mixture at concentrations found in occupational settings in order to understand their mechanism of action. The results obtained by air monitoring were below the occupational exposure limits for both substances. All biomarkers of effect, except for nucleoplasmic bridges, had higher mean values in workers (N = 17) compared to the corresponding controls (N = 17). There were statistically significant associations between exposed individuals and the presence of nuclear buds and oxidative damage. As for in vitro results, there was no significant influence on primary DNA damage in blood cells as evaluated by the comet assay. On the contrary, we did observe a significant increase of micronuclei and nuclear buds, but not nucleoplasmic bridges upon in vitro exposure. Taken together, both styrene and xylene have the potential to induce genomic instability either alone or in combination, showing higher effects when combined. The obtained data suggested that thresholds for individual chemicals might be insufficient for ensuring the protection of human health.

The circadian clock protects against acute radiation-induced dermatitis

Radiation-induced dermatitis is a common occurrence in cancer patients undergoing radiation therapy (RT) and is caused when ionizing radiation (IR) induces DNA strand breaks in skin cells. The wide use of RT in cancer treatments makes it important to minimize RT-induced toxicities including radiodermatitis. This study sought to determine if the circadian clock plays a protective role in minimizing radiodermatitis. We treated mice in control (Day Shift), environmentally-disrupted (Rotating Shift) and genetically-disrupted (Per 1/2−/−) circadian conditions with 6 Gy of IR to the whole body. There was a significantly increased number of radiodermatitis spots on mice with circadian clock disruption compared to control mice. Additionally, circadian clock disrupted mice exhibited reduced protein levels of Bmal1, a phenomenon that sensitized circadian synchronized keratinocytes to IR-induced DNA damage. Furthermore, the skin phenotype results corresponded with significantly reduced body weights and increased genomic DNA damage in blood cells of mice with clock disruption compared to control mice. These findings suggest that the circadian clock plays a protective role in IR-induced DNA damage and skin toxicity, possibly through BMAL1-dependent mechanisms, and potentially impacts RT-associated radiodermatitis in cancer patients.

BIOMONITORING OF A POPULATION RESIDING NEAR TO MINE TAILINGS IN GUANAJUATO, MEXICO

Some metals present in residues coming from mining activities can damage DNA. A preliminary evaluation was carried out to determine the genotoxic effects on a resident population from a mining area in Xichú, Guanajuato, Mexico. Blood lead levels (BLL), and arsenic levels in urine (AsU), were measured as biomarkers of exposure. Hematological damage was evaluated trough hematocrit, hemoglobin and activity of enzyme delta-aminolevulinic dehydratase (δ-ALAD). DNA damage in blood cells was evaluated by comet assay. BLL (7.5 ± 1.2 and 7.9 ± 3.3 μg/dL) and AsU (25.2 ± 15.8 and 18.3 ± 18.4 μg/g creatinine) were found in children and adults, respectively. Of the children and adults, 100 and 91.7 %, respectively had levels of enzyme activity below 20 U/L erythrocytes. Regarding DNA damage, the children showed an Olive tail moment of 5.0 ± 1.6 and a tail length of 40.9 ± 4.9 μm, of similar magnitude than adults (4.6 ± 1.0 and 41.8 ± 5.9 μm, respectively). In conclusion, this preliminary study describes the health risk scenario of population near the mine, nevertheless, more studies are needed in the area.

Effect of quinestrol on body weight, vital organs, biochemicals and genotoxicity in adult male lesser bandicoot rat, Bandicota bengalensis

The present study was aimed to evaluate the toxic effects of quinestrol (a synthetic estradiol) in male lesser bandicoot rat, Bandicota bengalensis. Effect was studied on body weight, weight of vital organs, changes in level of biochemical parameters and genotoxicity. Feeding of bait containing 0.01% quinestrol in bi-choice and 0.02 and 0.03% quinestrol in no-choice for a period of 10 days resulted in total ingestion of 19.50, 67.60 and 243.30 mg/kg bwt, respectively of the active ingredient. Autopsy of rats after 15 and 30 days of treatment withdrawal revealed no significant effect on body weight and weights of vital organs of rats. A significant decrease in the testicular levels of 17-beta hydroxysteroid dehydrogenase and increase in total soluble proteins was observed in rats treated with 0.02 and 0.03% quinestrol. The plasma levels of lipid peroxidation in the form of malondialdehyde concentration and lactate dehydrogenase increased significantly whereas the level of testosterone decreased significantly in treated rats. The plasma levels of acid and alkaline phosphatases, superoxide dismutase and total proteins differed non-significantly among rats of treated and untreated groups. The effect was found reversed partially in rats autopsied after 60 days of treatment withdrawal. No micronuclei in bone marrow cells, no aberrations in chromosomes and no DNA damage in blood cells during comet assay indicated no genotoxic effect of quinestrol on B. bengalensis at the test doses administered. The results thus revealed that quinestrol causes reversible toxic effects in the form of oxidative stress, increased lytic enzyme activity and decreased steroidogenesis which may further lead to testicular damage thereby inhibiting reproductive function. Also more effect was shown at higher doses ingested in no-choice test as compared to low doses ingested in bi-choice tests.

Functionality and DNA-damage properties of blood cells in lactating cows exposed to glyphosate contaminated feed at different feed energy levels

ABSTRACTGlyphosate (GL) inhibits the aromatic amino acid biosynthesis in plants and is worldwide the most used non-selective herbicide. Less is known about in vivo effects of GL contaminated feedstuffs on the health of dairy cows. The aim of this study was to examine the effects of GL residues in feed at different concentrate feed proportions (CFP) on haematology, immunological and redox parameters and on DNA-damage of blood cells in lactating dairy cows. During a 16-trial, 61 German Holstein cows (207 ± 49 d in milk; mean ± SD) were fed the same ration in week 0. Afterwards, they were assigned to either a group receiving a GL contaminated or a group receiving an uncontaminated total mixed ration (CON). Each group was subdivided into a “low concentrate” group (LC) and a “high concentrate” group (HC) with an energy content of 6.63 MJ NEL and 7.18 MJ NEL/kg dry matter, respectively. The diets were offered for ad libitum consumption. Blood samples were taken at weeks 0, 4, 8, 12 and 16. All blood samples were analysed for white and red blood cell counts. T-cell subpopulations, oxidative burst capability of leukocytes, apoptosis rate, phagocytic activity, activities of superoxide dismutase and glutathione peroxidase, the total non-enzymatic antioxidative capacity, viability and stimulation capacity of peripheral blood mononuclear cells and micronucleus- and comet assay on bovine leukocytes were measured only in week 16. The average individual GL intake of groups CON, GLLC and GLHC was 1.2 µg, 112.6 µg and 132.8 µg per kg body weight and day, respectively. GL contamination did not affect any of the tested parameters whereas CFP and time-influenced leukocytes, granulocytes, red blood cells, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin and CD4+ T-cells in an interactive manner characterised by a time-dependent increase in HC groups. It can be concluded that GL and GL in combination with different CFP showed no influence on any of the tested endpoints, whereas CFP and time influenced most parameters in an interactive manner.

The results of medical and psychophysiological examination performed during an arctic world oceanic international flight

Background: The development of the Arctic region is connected with extreme and strenuous work conditions and transmeridian shifts. The resulting stress changes the functional state of involved professionals irrespective of their age. Successful performance of job tasks depends on individual adaptation, which is an urgent issue to be studied with modern research methods.&#x0D; Aims: The study was a complex research project on adaptation and changes of cardiovascular and psychophysiological functioning in response to long-term stress associated with rapid climate changes and transmeridian shifts experienced by the participants of the Arctic World Oceanic International Flight Sever Vash.&#x0D; Materials and methods: The participants of Sever Vash expedition, which took place in July and August 2018, were examined. According to the design of the study, they underwent a complex laboratory and instrumental assessment before the start and immediately on the finish. Blood parameters, level of DNA damage in blood cells, cardiovascular parameters (heart rate, brachial and aortic blood pressure (BP), subendocardial blood flow etc.), allostatic load index (ALI), and data of psychophysiological tests with work capacity assessment were analyzed.&#x0D; Results: All participants (7 males, 3969 y.o.) completed the planned route. The actual duration of the flight was 43 days. Comparative pairwise analysis on the finish revealed an increase of total blood protein (p0.000), creatinine (p0.000), bilirubine (p=0.038) and AcAT (p=0.031), and glucose (p0.000) levels, and shifts in peripheral blood parameters, which are typical for the process of adaptation to the Polar conditions and transmeridian shifts. An increase of DNA damage in white blood cells was found. Average values of hemodynamic parameters were in a normal range; heart rate increased (p0.000); mean brachial BP (p=0.003) and systolic aortic BP (p=0.001) decreased. Average values of pulse BP and subendocardial blood flow did not change (p0.05). ALI increased in four pilots; in others, no ALI dynamic was observed. Psychophysiological potential decreased after the flight. The number of errors and omissions of target signal (р0.000) increased, attention span and emotional stability deteriorated. Along with this, the mood parameter increased to a maximum level, and risk tolerance level decreased (р0.001).&#x0D; Conclusions: Working in Arctic conditions is connected with stress factors and leads to multiple and deep changes required for urgent adaptation. Allostatic load index, which is an integral parameter of strained functioning in extreme conditions, can be a marker of individual adaptation. The achieved functional stability of body systems, particularly the cardiovascular system, ensures an acceptable level of work capacity in the considered conditions.

Apoptosis, reactive oxygen species and DNA damage in Familial Mediterranean Fever patients

BackgroundAssessment of apoptosis by flow cytometry assay and expression of apoptosis-related genes by quantitative Real-Time PCR has been suggested for predicting the patient response to therapeutic regimes of Familial Mediterranean Fever (FMF), as well as patient's survival. Therefore, the main objective of this study was to investigate the association of ROS generation on changes in apoptosis levels and expression of apoptosis related genes (Bcl2, Bax and Caspase-2) in FMF patients to get general profiling of this disease to use the most appropriate therapeutic strategy. Material and methodsThe study includes 40 Egyptian patients who were diagnosed with FMF according to Tel-Hashomer criteria. Blood samples of healthy controls were collected from 40 volunteers. Mutational analysis has been performed to confirm the inheritance of FMF. The collected samples of FMF patients and healthy controls were used to investigate the apoptosis rate, mRNA of apoptosis related genes (Bcl2, Bax and Caspase-2), reactive oxygen species (ROS) and DNA damage. ResultsWe found significant increase in apoptosis rates and elevated expression levels of apoptosis related genes in FMF patients. Moreover, the mean values of intracellular ROS generation and DNA damage in blood cells of FMF patients were significantly higher than in the control cohorts. ConclusionThe ROS production could be involved in oxidative modification of cellular DNA, modulation of apoptotic gene expression, and promoting cell death in FMF patients.

Synergistic improved efficacy of Gymnadenia orchidis root Salep and pumpkin seed on induced diabetic complications

ObjectiveDiabetes mellitus occurs due to either deficiency of insulin or resistance to insulin. Synthetic drugs and insulin therapy against diabetes possess numerous drawbacks. Diabetic people are advised to choose low-glycemic food and herbal products to control diabetes. This study aims to examine the synergistic effects of aqueous root Salep ofGymnadenia orchidis Lindl and pumpkin seed powder on Streptozotocin induced diabetic mice. MethodsOut of 6 groups, animals in 2 groups were kept as control and rest 4 groups were made diabetic by Streptozotocin. Animals in one diabetic group were supplemented with effective dose (200 mg/kg of body weight) of root Salep, one with pumpkin seed powder (5%) mixed food, and another with Salep and pumpkin seed food. Changes in various biochemical parameters, DNA damage and liver and kidney structures were noted after 21 days treatment. ResultsSalep with pumpkin seed supplementation significantly normalized the alterations of different biochemical parameters of diabetic mice. The DNA damage in blood cells of diabetic mice was recovered by this supplementation. Terpenoids of root Salep and anti-oxidants of pumpkin seed may play the active role against diabetes. ConclusionThe root Salep and pumpkin seed synergistically prevent diabetic complications and could be better supplementation against type-2 diabetes.

Triple-mixture of Zn, Mn, and Fe increases bioaccumulation and causes oxidative stress in freshwater neotropical fish.

Metal bioaccumulation and oxidative stress biomarkers were determined in Prochilodus lineatus to understand the effects of short-term exposure to a triple-mixture of Zn, Mn, and Fe. Three independent tests were carried out, in which fish were exposed to 3 concentrations of Zn (0.18, 1.0, and 5.0 mg L-1 ), Mn (0.1, 0.5, and 5.0 mg L-1 ), and in the mix test to Fe (5.0 mg L-1 ) and a mixture of Zn (1.0 mg L-1 ) + Mn (0.5 mg L-1 ), with and without Fe. After exposure for 96 h, tissues were removed for metal bioaccumulation analysis and oxidative stress biomarkers were determined in liver, along with DNA damage in blood cells. Our results revealed that Zn and Mn were bioaccumulated in fish tissues after exposure to 5.0 mg L-1 , whereas Fe only bioaccumulated in muscle and gills after mixture exposure. Results indicated that 1 metal interfered with the other's bioaccumulation. In P. lineatus, 5 mg L-1 of both Mn and Fe were toxic, because damage was observed (lipid peroxidation [LPO] in liver and DNA damage in blood cells), whereas Zn induced liver responses (metallothionein [MT] and reduced glutathione [GSH] increases) to prevent damage. In terms of bioaccumulation and alterations of oxidative stress biomarkers, we showed that Zn, Mn, and Fe triple-mixture enhances individual metal toxicity in Neotropical fish P. lineatus. Environ Toxicol Chem 2018;37:1749-1756. © 2018 SETAC.

The impact of iodinated contrast media on intravascular and extravascular absorbed doses in X-ray imaging: A microdosimetric analysis

Studies suggest iodinated contrast media (ICM) may increase organ dose and blood cell DNA damage for a given X-ray exposure. The impact of ICM on dose/damage to extravascular cells and cancer risks is unclear. MethodsWe used Monte Carlo modelling to investigate the microscopic distribution of absorbed dose outside the lumen of arteries, capillaries and interstitial fluids containing blood and various concentrations of iodine. Models were irradiated with four X-ray spectra representing clinical procedures. ResultsFor the artery model, The average dose enhancement factors (DEF) to blood were 1.70, 2.38, 7.38, and 12.34 for mass concentrations of iodine in blood (ρiI) of 5, 10, 50 and 100 mg/ml, respectively, compared to 0 mg/ml. Average DEFs were reduced to 1.26, 1.51, 3.48 and 5.56, respectively, in the first micrometre of the vessel wall, falling to 1.01, 1.02, 1.06 and 1.09 at 40–50 μm from the lumen edge. For the capillary models, DEF for extravascular tissues was on average 48% lower than DEF for the whole model, including capillaries. A similar situation was observed for the interstitial model, with DEF to the cell nucleus being 35% lower than DEF for the whole model. ConclusionsWhile ICM may modify the absorbed doses from diagnostic X-ray examinations, the effect is smaller than suggested by assays of circulating blood cells or blood dose enhancement. Conversely, the potentially large increase in dose to the endothelium of blood vessels means that macroscopic organ doses may underestimate the risk of radiation induced cardiovascular disease for ICM-enhanced exposures.

DNA damage in blood cells in relation to chemotherapy and nutritional status in colorectal cancer patients—A pilot study

DNA damage can be considered as a biomarker for toxicity and response to chemotherapy. It is not known whether the chemotherapy-induced genotoxicity is associated with malnutrition. In this pilot study, we assess genotoxicity by means of DNA damage in patients with lymph-node positive colorectal cancer (CRC) and explore associations with chemotherapy treatment and nutritional status. DNA damage was compared between patients receiving chemotherapy (n = 24) and those not receiving chemotherapy (n = 20). DNA damage was measured in frozen whole blood by the comet assay. Associations between DNA damage and various indicators of malnutrition were also explored, including Patient-Generated Subjective Global Assessment (PG-SGA), bioelectrical impedance analysis (BIA) and anthropometric measurements, using multiple linear regression models. Patients on chemotherapy have higher levels of DNA damage in blood cells than patients not receiving chemotherapy (median of 16.9 and 7.9% tail DNA respectively, p = 0.001). The moderately malnourished patients (PG-SGA category B), representing 41% of the patients, have higher levels of cellular DNA damage than patients with good nutritional status (mean difference of 7.5% tail DNA, p = 0.033). In conclusion, adjuvant chemotherapy and malnutrition are both associated with increased levels of DNA damage in blood cells of CRC patients. Carefully controlled longitudinal studies or randomized controlled trials should be performed to determine whether good nutritional status may protect against chemotherapy-induced genotoxicity and enhance compliance to therapy in CRC patients.

Genetic variation and risk of DNA damage in peripheral blood lymphocytes of Iranian formaldehyde-exposed workers.

Formaldehyde (FA) has given positive results for the genetic damage evaluated in human peripheral blood lymphocytes. Polymorphism plays a special role in the toxicity of chemicals. DNA damage in blood cells was evaluated in workers who were occupationally exposed to FA. This study tested the association of alcohol dehydrogenase III (ADH3) and manganese-superoxide dismutase (Mn-SOD) gene polymorphism, with DNA damage of peripheral blood lymphocytes. Gene polymorphisms were evaluated in 54 workers from melamine dinnerware workshops and 34 workers from dairy production workshops. The control and exposed population were matched based on age, smoking, work history and socioeconomic status. DNA damage was evaluated by alkaline comet assay in the peripheral blood lymphocytes. ADH3 and Mn-SOD genotypes were determined in all workers using polymerase chain reaction-restriction fragment length polymorphism method. DNA damage of lymphocyte cells was significantly higher ( p < 0.001) in the exposed individuals in comparison with the control population. The examinations of the exposed group had revealed significantly higher ( p < 0.01) variant of Val/Val of Mn-SOD compared to control group. In workers with ADH32-2 variant, significantly higher levels of DNA damage ( p < 0.01) were observed than the control population with the same genotype. It could be concluded that enzymes involved in the metabolism of FA and oxidative stress controlling are two important effective parameters for DNA damage of peripheral blood lymphocytes in exposed people. These results are regarded as a pioneer investigation for the management of health risks assessment.

PT08.1: DNA Damage in Blood Cells in Relation to Chemotherapy and Nutritional Status in Colorectal Cancer Patients

PT08.1: DNA Damage in Blood Cells in Relation to Chemotherapy and Nutritional Status in Colorectal Cancer Patients

The impact of multiple stressors on the biomarkers response in gills and liver of freshwater breams during different seasons

Biomarkers attract increasing attention in environmental studies, as a tool for detection of exposure and effects of pollution, from both natural and anthropogenic sources. This study aims to assess the impact of multiple stressors during distinctive seasons, covering also extreme hydrological events (extensive flooding in the mid May 2014), on different levels of biological organization in the liver and gills of three closely related freshwater breams. Our previous study on DNA damage in blood cells of these specimens showed increased DNA damage in June 2014, one month after the flooding event. As a continuation of that research, the present study was conducted. As a biomarker of exposure DNA damage was measured by applying the alkaline comet assay, while histopathological alterations were monitored as a biomarker of effect. Additionally, concentrations of metals and metalloids in gills, liver and muscle were assessed. Sampling of fish tissues was performed in 2014, during winter (January and February), spring (March and early June) and summer (late June, July and August). Significant seasonal difference in DNA damage was observed for both tissues. During spring and summer the level of DNA damage in gills was significantly higher when compared to the liver. Histopathological analyses showed higher frequency of alterations in gills during spring, and in liver during summer, but without a significant seasonal difference. Gills had the highest concentration of metals and metalloids during the spring and summer, and liver during winter. Muscle was the least affected tissue during all three seasons. This study highlighted the importance of the multiple biomarker approach and the use of different fish tissues in assessment of surface water pollution.