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A biomonitoring study of mercury in hair and urine of 267 adults living in Madrid (Spain)
Abstracts / Toxicology Letters 180S (2008) S32–S246
Kralove, Czech Republic, 3 Clinic of Dermal and Venereal Diseases, University Hospital, Hradec Kralove, Czech Republic, 4 Institute of Clinical Biochemical and Diagnostic, University Hospital, Hradec Kralove, Czech Republic 5 Institute of Hygiene and Preventive Medicine, Charles University in Prague, Faculty of Hradec Kralove, Czech Republic Goeckerman regimen (GR) of psoriasis includes dermal application of crude coal tar (polycyclic aromatic hydrocarbons—PAHs) and exposure to UV radiation. PAHs and UV radiation represent mutagenic, carcinogenic and immunotoxic agents with pro-apoptotic effects. Apoptosis is a form of programmed cell death which may be induced via protein p53 or cytokines FasL. The aim of presented study was to evaluate plasma concentrations of p53 protein and soluble FasL in 20 patients with psoriasis (treated by GR). The urinary and blood samples were collected before and after GR. The level of PASI score (psoriasis area and Severity Index) was significantly decreased after GR (p < 0.001) and confirmed high efficiency of GR. Significantly increased level of 1-hydroxypyrene (p < 0.01) indicated high intensity of dermal penetration of PAHs. Significantly increased chromosomal aberrations in peripheral lymphocytes after GR (p < 0.001) confirmed genotoxic effect of this therapy. In addition, we found significantly increased protein p53 in plasma (p < 0.05), as an indicator of cell response to DNA damage, and significantly increased soluble FasL serum level (p < 0.01), as indicators of apoptosis after GR. All mentioned results indicated increased genotoxic and pro-apoptotic effect of GR. Acknowledgement: The work was supported by the Research project No. 00179906, Ministry of Health, Czech Republic. doi:10.1016/j.toxlet.2008.06.504 B10 Antioxidant capacity of Citrus hystrix leaf using in vitro methods and their anticlastogenic potential using the erythrocyte micronucleus assay in the mouse Chaniphun Butryee 1,∗ , Piengchai Kupradinun 2
S79
These results suggest that C. hystrix leaf exhibited in vitro antioxidant properties, while also having weakly anticlastogenic effects against both direct and indirect acting carcinogens, MMC and DMBA, respectively. However, it had no clastogenicity. doi:10.1016/j.toxlet.2008.06.505 B11 Urinary methyl tert-butyl ether as biomarker of exposure to urban traffic Laura Campo ∗ , Licia Scibetta, Paolo Costamagna, Piero E. Cirla, Federica Rossella, Lorenzo Patrini, Silvia Fustinoni Department of Occupational and Environmental Health, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy Methyl tert-butyl ether (MTBE) is an organic compound added to fuels to increase octane ratings and/or reduce carbon monoxide emissions, and for this reason, it is found in urban environments because of auto vehicular traffic. Aim of the present study was to evaluate the possibility of using excretion of urinary MTBE (UMTBE) as biomarker of exposure to traffic. With this aim, 127 Milan urban policemen, working as traffic wardens, and 90 controls were investigated. Spot urine samples were obtained before and at the end of the work shift and analysis of U-MTBE was performed by headspace-solid phase microextraction GC-MS. Median level of airborne MTBE for controls was 4 ng/m3 (range <0.5–528 g/m3 ), while no data were available for traffic wardens. Median excretion levels of U-MTBE in before and end-shift samples were 118 ng/L (50–657) and 147 ng/L (68–556) for traffic wardens and 42 ng/L (<10–763) and 78 ng/L (<10–483) for controls. Excretion levels were always significantly higher in traffic wardens than in controls, moreover significant differences were found between before- and end-shift samples in both groups (p < 0.01). Airborne and urinary levels were significantly correlated (r = 0.40, p < 0.01). Smoking did not affect the excretion of U-MTBE. The results of this study suggest that U-MTBE is a reliable marker for the assessment of exposure to urban traffic.
1
Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand, 2 National Cancer Institute, Bangkok, Thailand
doi:10.1016/j.toxlet.2008.06.506
The purpose of this study was to evaluate in vitro total antioxidant capacities (TAC) of Citrus hystrix leaf and assessed in vivo for its clastogenic and anticlastogenic potential using the erythrocyte micronucleus assay in the mouse. Water- and lipid-soluble extracts of freeze-dried C. hystrix were evaluated for antioxidant activities by 2 different assays, i.e. oxygen radical absorption capacity (ORAC) and ferric reducing/antioxidant power (FRAP). Regarding the clastogenic evaluation, freeze-dried sample was administered by gavage to mice at two doses (0.2 g/kg BW/day or 0.4 g/kg BW/day) over 14 days and their anticlastogenicity was evaluated on 7,12 dimethylbenz[a]anthracene (DMBA) (40 mg/kg BW) or mitomycin C (MMC) (1 mg/kg BW)-induced genotoxicity. Peripheral blood samples were collected at 0, 24, 48 h following treatment. The results demonstrated that the TAC values evaluated by ORAC and FRAP were shown to be 433 ± 30 M Trolox Equivalent/g and 95 ± 2 M Fe2+ Equivalent/g, respectively. The ingestion of 0.2 or 0.4 g/kg BW of samples, for 2 weeks had no significant effect on the micronucleus formation in erythrocyte micronucleus assay. Their anticlastogenic at the dose level 0.2 g/kg BW tended to reduce the clastogenic effects in MMC-treated and DMBA-treated groups at 24 and 48 h, respectively after administration of clastogens but they were not significantly different (p ≥ 0.05) when compared with the solvent control group.
B12 A biomonitoring study of mercury in hair and urine of 267 adults living in Madrid (Spain) ˜ 1,∗ , Carmen Navarro 1 , Ana Canas ˜ 1 , Gema Díaz 1 , Argelia Castano Jesús P. García 1 , Marta Esteban 1 , Miguel A. Lucena 3 , Misericordia Arribas 2 , José A. Jiménez 1 1
Environmental Toxicology, C.N.S.A. Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain, 2 Medical Unit, IS Carlos III, 28220 Majadahonda, Madrid, Spain, 3 Quality Assurance Unit, C.N.S.A. I.S. Carlos III, 28220 Majadahonda, Madrid, Spain Mercury is a natural occurring metal but most human exposure occurs as a consequence of human activities. Concerns about adverse health effects of environmental pollutants have lead to an increase in measures to control and protect general population. The use of biomarkers is now an accepted measure of chemical exposure in risk assessment. However, information on background exposures and biomarker concentrations of many environmental chemicals in the general population is limited. This study aims to determine reference ranges for several biomarkers of chemical exposure, measurable in urine, blood and hair, within the general adult Spanish population. The study will involve more than 2000
S80
Abstracts / Toxicology Letters 180S (2008) S32–S246
volunteers throughout Spain and is currently underway. Described here is a pilot study, carried out during June and September 2007 to test the study methodology and select human matrices for biomonitoring. The subgroup is formed by 267 volunteers of which 79% were female and 31% male. Participants were asked to complete a questionnaire and provide a urine and hair sample. The age of participants ranged from 21 to 69 years old. The initial results of the urinary concentrations for total mercury and hair concentration of total and methyl mercury are reported. The geometric mean hair mercury concentration was 2.23 g/g. Range of values was among 0.15 and 11.6 g/g. Mercury levels were associated with age, and fish consumption. Average levels found in this pilot study are higher than those found in other countries such as USA, Germany or Italy, but were in the range of some references found on Spanish population. doi:10.1016/j.toxlet.2008.06.507 B13 Baseline cytogenetic profiles of a healthy Turkish population by three test systems: Comparison between assays Erdem Coskun ∗ , Ela Kadioglu, Gonca Cakmak-Demircigil, Eren Ozcagli, Emre Durmaz, Bensu Karahalil, Sema Burgaz, Semra Sardas, Neslihan Aygun-Kocabas Gazi University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey The use of cytogenetic biomarkers for biomonitoring human populations is increasing in the last decades because of their sensitivity for measuring DNA damage caused by genotoxic agents and predictive value for cancer risk. Three most widely applied of these tests are the chromosomal aberration (CA), cytokinesis block micronucleus (MN) and comet (single cell gel electrophoresis) assays. Among these tests, CA assay and MN test on human lymphocytes have been well validated and their predictive value for assessing cancer risk in human has been proved by wide prospective cohort studies. It has great importance to better validate all these tests and to assess the association between them in terms of cancer risks for biomonitoring human populations and individuals. Therefore we examined, CA and MN frequencies and comet tail parameters in 105 healthy Turkish individuals (52M/53F, mean age: 32.1 ± 8.02). The mean frequencies for MN and CA (±S.D.) are 8.00 ± 6.01‰ and 0.92 ± 1.34%, respectively and the mean (±S.D.) tail intensity values for comet assay is 6.82 ± 2.07. MN frequencies are significantly correlated with CA (r = 0.538, p < 0.05) and with comet tail intensity (r = 0.274, p < 0.05) and CA frequencies are positively correlated with tail intensity (r = 0.140, p > 0.05). Even though the mechanisms of these tests are different, positive correlation between them emphasize the future of the use of cytogenetic biomarkers for screening populations, and individuals as the ultimate goal. Acknowledgement: This study was supported by Prime Ministry State Planning Organization, Scientific Research Fund (Project Number: 2003K120470-05). doi:10.1016/j.toxlet.2008.06.508
B14 Identifying candidate biomarkers of effects of deoxynivalenol exposure using proteomics André Nogueira da Costa 1,∗ , Renée Mijal 1 , Jeff Keen 2 , John Findlay 2 , Christopher Wild 1 1
Molecular Epidemiology Unit, Centre for Epidemiology and Biostatistics, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom, 2 Institute of Membrane and Systems Biology, Faculty of Biological Sciences, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom Deoxynivalenol (DON) is a mycotoxin that contaminates cereals worldwide. Recent studies indicate DON is common in the Western European diet. At high doses, DON is reported to induce acute gastrointestinal toxicity. At low chronic doses (typical of the diet), little is known about effects in humans. The long-term objective of this study is to determine in population based studies whether low dose, chronic exposure to DON affects immune function. To achieve this objective, proteomics is used to develop candidate biomarkers of effect for DON in human B (RPMI1788) and T (JurkatE6.1) lymphoblasts. Both cell types were maintained at a density of 3 × 105 cells/mL and exposed to DON (up to 500 ng DON/mL) for 24h for cytotoxicity experiments and proteomic studies. Cell toxicity was assessed using the MTT assay. TwoDimensional gel electrophoresis was used to compare proteomic profiles in whole cell lysates of human B and T lymphoblasts. Proteins were identified through MALDI-TOF. Consistent with previous reports, cytotoxic effects (≥20%) were achieved at 250 ng DON/mL and 500 ng DON/mL in T and B lymphoblasts, respectively. Analysis of proteomic profiles conducted in T lymphoblasts suggest that seven spots exhibited a >1.5-fold change in response to treatment, reproducible in three separate experiments repeated in triplicate. Protein identification is being conducted. Preliminary results with B lymphoblasts suggest analogous alterations occur in the protein patterns, allowing for additional protein identification. Further investigation is required to validate and elucidate the importance of the detected proteomic changes. doi:10.1016/j.toxlet.2008.06.509 B15 Evaluation of plasma nitrite/nitrate levels in prostate cancer, benign prostatic hyperplasia patients and healthy individuals Ayse Eken 1,∗ , Ahmet Aydin 1 , Ahmet Sayal 1 , Onur Erdem 1 , Zorica Arsova-Sarafinovska 2 , Aleksandar Dimovski 2 , Ayhan Savaser 1 , Yasar Ozgok 3 , Koray Erten 3
1
Gülhane Military Medical Academy, Department of Toxicology, Ankara, Turkey, 2 Faculty of Pharmacy, Institute of Pharmaceutical Chemistry, Skopje, The Former Yugolav Republic of Macedonia, 3 Gülhane Military Medical Academy, Department of Urology, Ankara, Turkey Prostate cancer and benign prostatic hyperplasia (BPH) are common diseases in aging men that are associated with considerable morbidity, including the risk of acute urinary retention and the need for surgery. The nitric oxide (NO• ) is a not stable radical and converted to nitrite/nitrate anion (NO2 − /NO3 − ) in a very short time, which is more stable product. NO production may promote cancer progression by providing a selective growth advantage to tumor cells, by angiogenic stimulus and by direct DNA damage. In this study our aim was to investigate the plasma NO2 − /NO3 − levels in patients with prostate cancer, BPH, and control subjects. Blood
Kralove, Czech Republic, 3 Clinic of Dermal and Venereal Diseases, University Hospital, Hradec Kralove, Czech Republic, 4 Institute of Clinical Biochemical and Diagnostic, University Hospital, Hradec Kralove, Czech Republic 5 Institute of Hygiene and Preventive Medicine, Charles University in Prague, Faculty of Hradec Kralove, Czech Republic Goeckerman regimen (GR) of psoriasis includes dermal application of crude coal tar (polycyclic aromatic hydrocarbons—PAHs) and exposure to UV radiation. PAHs and UV radiation represent mutagenic, carcinogenic and immunotoxic agents with pro-apoptotic effects. Apoptosis is a form of programmed cell death which may be induced via protein p53 or cytokines FasL. The aim of presented study was to evaluate plasma concentrations of p53 protein and soluble FasL in 20 patients with psoriasis (treated by GR). The urinary and blood samples were collected before and after GR. The level of PASI score (psoriasis area and Severity Index) was significantly decreased after GR (p < 0.001) and confirmed high efficiency of GR. Significantly increased level of 1-hydroxypyrene (p < 0.01) indicated high intensity of dermal penetration of PAHs. Significantly increased chromosomal aberrations in peripheral lymphocytes after GR (p < 0.001) confirmed genotoxic effect of this therapy. In addition, we found significantly increased protein p53 in plasma (p < 0.05), as an indicator of cell response to DNA damage, and significantly increased soluble FasL serum level (p < 0.01), as indicators of apoptosis after GR. All mentioned results indicated increased genotoxic and pro-apoptotic effect of GR. Acknowledgement: The work was supported by the Research project No. 00179906, Ministry of Health, Czech Republic. doi:10.1016/j.toxlet.2008.06.504 B10 Antioxidant capacity of Citrus hystrix leaf using in vitro methods and their anticlastogenic potential using the erythrocyte micronucleus assay in the mouse Chaniphun Butryee 1,∗ , Piengchai Kupradinun 2
S79
These results suggest that C. hystrix leaf exhibited in vitro antioxidant properties, while also having weakly anticlastogenic effects against both direct and indirect acting carcinogens, MMC and DMBA, respectively. However, it had no clastogenicity. doi:10.1016/j.toxlet.2008.06.505 B11 Urinary methyl tert-butyl ether as biomarker of exposure to urban traffic Laura Campo ∗ , Licia Scibetta, Paolo Costamagna, Piero E. Cirla, Federica Rossella, Lorenzo Patrini, Silvia Fustinoni Department of Occupational and Environmental Health, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy Methyl tert-butyl ether (MTBE) is an organic compound added to fuels to increase octane ratings and/or reduce carbon monoxide emissions, and for this reason, it is found in urban environments because of auto vehicular traffic. Aim of the present study was to evaluate the possibility of using excretion of urinary MTBE (UMTBE) as biomarker of exposure to traffic. With this aim, 127 Milan urban policemen, working as traffic wardens, and 90 controls were investigated. Spot urine samples were obtained before and at the end of the work shift and analysis of U-MTBE was performed by headspace-solid phase microextraction GC-MS. Median level of airborne MTBE for controls was 4 ng/m3 (range <0.5–528 g/m3 ), while no data were available for traffic wardens. Median excretion levels of U-MTBE in before and end-shift samples were 118 ng/L (50–657) and 147 ng/L (68–556) for traffic wardens and 42 ng/L (<10–763) and 78 ng/L (<10–483) for controls. Excretion levels were always significantly higher in traffic wardens than in controls, moreover significant differences were found between before- and end-shift samples in both groups (p < 0.01). Airborne and urinary levels were significantly correlated (r = 0.40, p < 0.01). Smoking did not affect the excretion of U-MTBE. The results of this study suggest that U-MTBE is a reliable marker for the assessment of exposure to urban traffic.
1
Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand, 2 National Cancer Institute, Bangkok, Thailand
doi:10.1016/j.toxlet.2008.06.506
The purpose of this study was to evaluate in vitro total antioxidant capacities (TAC) of Citrus hystrix leaf and assessed in vivo for its clastogenic and anticlastogenic potential using the erythrocyte micronucleus assay in the mouse. Water- and lipid-soluble extracts of freeze-dried C. hystrix were evaluated for antioxidant activities by 2 different assays, i.e. oxygen radical absorption capacity (ORAC) and ferric reducing/antioxidant power (FRAP). Regarding the clastogenic evaluation, freeze-dried sample was administered by gavage to mice at two doses (0.2 g/kg BW/day or 0.4 g/kg BW/day) over 14 days and their anticlastogenicity was evaluated on 7,12 dimethylbenz[a]anthracene (DMBA) (40 mg/kg BW) or mitomycin C (MMC) (1 mg/kg BW)-induced genotoxicity. Peripheral blood samples were collected at 0, 24, 48 h following treatment. The results demonstrated that the TAC values evaluated by ORAC and FRAP were shown to be 433 ± 30 M Trolox Equivalent/g and 95 ± 2 M Fe2+ Equivalent/g, respectively. The ingestion of 0.2 or 0.4 g/kg BW of samples, for 2 weeks had no significant effect on the micronucleus formation in erythrocyte micronucleus assay. Their anticlastogenic at the dose level 0.2 g/kg BW tended to reduce the clastogenic effects in MMC-treated and DMBA-treated groups at 24 and 48 h, respectively after administration of clastogens but they were not significantly different (p ≥ 0.05) when compared with the solvent control group.
B12 A biomonitoring study of mercury in hair and urine of 267 adults living in Madrid (Spain) ˜ 1,∗ , Carmen Navarro 1 , Ana Canas ˜ 1 , Gema Díaz 1 , Argelia Castano Jesús P. García 1 , Marta Esteban 1 , Miguel A. Lucena 3 , Misericordia Arribas 2 , José A. Jiménez 1 1
Environmental Toxicology, C.N.S.A. Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain, 2 Medical Unit, IS Carlos III, 28220 Majadahonda, Madrid, Spain, 3 Quality Assurance Unit, C.N.S.A. I.S. Carlos III, 28220 Majadahonda, Madrid, Spain Mercury is a natural occurring metal but most human exposure occurs as a consequence of human activities. Concerns about adverse health effects of environmental pollutants have lead to an increase in measures to control and protect general population. The use of biomarkers is now an accepted measure of chemical exposure in risk assessment. However, information on background exposures and biomarker concentrations of many environmental chemicals in the general population is limited. This study aims to determine reference ranges for several biomarkers of chemical exposure, measurable in urine, blood and hair, within the general adult Spanish population. The study will involve more than 2000
S80
Abstracts / Toxicology Letters 180S (2008) S32–S246
volunteers throughout Spain and is currently underway. Described here is a pilot study, carried out during June and September 2007 to test the study methodology and select human matrices for biomonitoring. The subgroup is formed by 267 volunteers of which 79% were female and 31% male. Participants were asked to complete a questionnaire and provide a urine and hair sample. The age of participants ranged from 21 to 69 years old. The initial results of the urinary concentrations for total mercury and hair concentration of total and methyl mercury are reported. The geometric mean hair mercury concentration was 2.23 g/g. Range of values was among 0.15 and 11.6 g/g. Mercury levels were associated with age, and fish consumption. Average levels found in this pilot study are higher than those found in other countries such as USA, Germany or Italy, but were in the range of some references found on Spanish population. doi:10.1016/j.toxlet.2008.06.507 B13 Baseline cytogenetic profiles of a healthy Turkish population by three test systems: Comparison between assays Erdem Coskun ∗ , Ela Kadioglu, Gonca Cakmak-Demircigil, Eren Ozcagli, Emre Durmaz, Bensu Karahalil, Sema Burgaz, Semra Sardas, Neslihan Aygun-Kocabas Gazi University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey The use of cytogenetic biomarkers for biomonitoring human populations is increasing in the last decades because of their sensitivity for measuring DNA damage caused by genotoxic agents and predictive value for cancer risk. Three most widely applied of these tests are the chromosomal aberration (CA), cytokinesis block micronucleus (MN) and comet (single cell gel electrophoresis) assays. Among these tests, CA assay and MN test on human lymphocytes have been well validated and their predictive value for assessing cancer risk in human has been proved by wide prospective cohort studies. It has great importance to better validate all these tests and to assess the association between them in terms of cancer risks for biomonitoring human populations and individuals. Therefore we examined, CA and MN frequencies and comet tail parameters in 105 healthy Turkish individuals (52M/53F, mean age: 32.1 ± 8.02). The mean frequencies for MN and CA (±S.D.) are 8.00 ± 6.01‰ and 0.92 ± 1.34%, respectively and the mean (±S.D.) tail intensity values for comet assay is 6.82 ± 2.07. MN frequencies are significantly correlated with CA (r = 0.538, p < 0.05) and with comet tail intensity (r = 0.274, p < 0.05) and CA frequencies are positively correlated with tail intensity (r = 0.140, p > 0.05). Even though the mechanisms of these tests are different, positive correlation between them emphasize the future of the use of cytogenetic biomarkers for screening populations, and individuals as the ultimate goal. Acknowledgement: This study was supported by Prime Ministry State Planning Organization, Scientific Research Fund (Project Number: 2003K120470-05). doi:10.1016/j.toxlet.2008.06.508
B14 Identifying candidate biomarkers of effects of deoxynivalenol exposure using proteomics André Nogueira da Costa 1,∗ , Renée Mijal 1 , Jeff Keen 2 , John Findlay 2 , Christopher Wild 1 1
Molecular Epidemiology Unit, Centre for Epidemiology and Biostatistics, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom, 2 Institute of Membrane and Systems Biology, Faculty of Biological Sciences, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom Deoxynivalenol (DON) is a mycotoxin that contaminates cereals worldwide. Recent studies indicate DON is common in the Western European diet. At high doses, DON is reported to induce acute gastrointestinal toxicity. At low chronic doses (typical of the diet), little is known about effects in humans. The long-term objective of this study is to determine in population based studies whether low dose, chronic exposure to DON affects immune function. To achieve this objective, proteomics is used to develop candidate biomarkers of effect for DON in human B (RPMI1788) and T (JurkatE6.1) lymphoblasts. Both cell types were maintained at a density of 3 × 105 cells/mL and exposed to DON (up to 500 ng DON/mL) for 24h for cytotoxicity experiments and proteomic studies. Cell toxicity was assessed using the MTT assay. TwoDimensional gel electrophoresis was used to compare proteomic profiles in whole cell lysates of human B and T lymphoblasts. Proteins were identified through MALDI-TOF. Consistent with previous reports, cytotoxic effects (≥20%) were achieved at 250 ng DON/mL and 500 ng DON/mL in T and B lymphoblasts, respectively. Analysis of proteomic profiles conducted in T lymphoblasts suggest that seven spots exhibited a >1.5-fold change in response to treatment, reproducible in three separate experiments repeated in triplicate. Protein identification is being conducted. Preliminary results with B lymphoblasts suggest analogous alterations occur in the protein patterns, allowing for additional protein identification. Further investigation is required to validate and elucidate the importance of the detected proteomic changes. doi:10.1016/j.toxlet.2008.06.509 B15 Evaluation of plasma nitrite/nitrate levels in prostate cancer, benign prostatic hyperplasia patients and healthy individuals Ayse Eken 1,∗ , Ahmet Aydin 1 , Ahmet Sayal 1 , Onur Erdem 1 , Zorica Arsova-Sarafinovska 2 , Aleksandar Dimovski 2 , Ayhan Savaser 1 , Yasar Ozgok 3 , Koray Erten 3
1
Gülhane Military Medical Academy, Department of Toxicology, Ankara, Turkey, 2 Faculty of Pharmacy, Institute of Pharmaceutical Chemistry, Skopje, The Former Yugolav Republic of Macedonia, 3 Gülhane Military Medical Academy, Department of Urology, Ankara, Turkey Prostate cancer and benign prostatic hyperplasia (BPH) are common diseases in aging men that are associated with considerable morbidity, including the risk of acute urinary retention and the need for surgery. The nitric oxide (NO• ) is a not stable radical and converted to nitrite/nitrate anion (NO2 − /NO3 − ) in a very short time, which is more stable product. NO production may promote cancer progression by providing a selective growth advantage to tumor cells, by angiogenic stimulus and by direct DNA damage. In this study our aim was to investigate the plasma NO2 − /NO3 − levels in patients with prostate cancer, BPH, and control subjects. Blood