Lead and Arsenic Levels in Women with Different Body Mass Composition

The objective of this study was to evaluate whether lead (Pb) and arsenic (As) levels in biological fluids were associated to the body composition in a group of reproductive-age women. Voluntary childbearing-age women (n = 107) were divided into three groups according to their body mass index (BMI: weight/height² (kg/m²): low weight (BMI<18.5 kg/m²), normal $ \left( {{\text{BMI}} > 19\kern1.5pt<\kern1.5pt24.9\,{{\text{kg}} \mathord{\left/{\vphantom {{\text{kg}} {{{\text{m}}^{\text{2}}}}}} \right.} {{{\text{m}}^{\text{2}}}}}} \right) $ \left( {{\text{BMI}} > 19\kern1.5pt<\kern1.5pt24.9\,{{\text{kg}} \mathord{\left/{\vphantom {{\text{kg}} {{{\text{m}}^{\text{2}}}}}} \right.} {{{\text{m}}^{\text{2}}}}}} \right) , and overweight (BMI>25 kg/m²). Body composition and fat mass percentage were determined by the isotopic dilution method utilizing deuterated water. Blood lead concentrations were determined by graphite furnace atomic absorption spectrometry and urinary arsenic (AsU) concentrations by inductively coupled plasma mass spectrometry. The type and frequency of food consumption and lifestyle-related factors were also registered. Most women had $ {\text{PbB}}\,{\text{levels}} > 2\kern1.5pt<\kern1.5pt10\,{\mu{{\text{ g}}} \mathord{\left/{\vphantom {\mu{{\text{ g}}} {\text{dL}}}} \right.} {\text{dL}}} $ {\text{PbB}}\,{\text{levels}} > 2\kern1.5pt<\kern1.5pt10\,{\mu{{\text{ g}}} \mathord{\left/{\vphantom {\mu{{\text{ g}}} {\text{dL}}}} \right.} {\text{dL}}} , and only 2.6% had AsU concentrations above 50 μg/L. The levels of these toxic elements were not found to be associated with the fat mass percentage.     

Activity of glutathione peroxidase, glutathione reductase, and lipid peroxidation in erythrocytes in workers exposed to lead

The aim of this study was to estimate the activity of glutathione peroxidase (GPx), glutathione reductase (GR), and malondialdehyde (MDA) in erythrocytes in healthy male employees of zinc and lead steelworks who were occupationally exposed to lead over a long period of time (about 15 yr). Workers were divided into two subgroups: the first included employees with low exposure to lead (LL) (n=75) with blood lead level PbB=25–40 μg/dL and the second with high exposure to lead (HL) (n=62) with PbB over 40 μg/dL. Administration workers (n=35) with normal levels of PbB and zinc protoporphyrin in blood (ZPP) in blood were the control group. The activity of GPx significantly increased in LL when compared to the control group (p<0.001) and decreased when compared to the HL group (p=0.036). There were no significant changes in activity of GR in the study population. MDA erythrocyte concentration significantly increased in the HL group compared to the control (p=0.014) and to the LL group (p=0.024). For the people with low exposure to lead (PbB=25–40 μg/dL), the increase of activity of GPx by about 79% in erythrocytes prevented lipid peroxidation and it appears to be the adaptive mechanism against the toxic effect of lead. People with high exposure to lead (with PbB over 40 μg/dL) have shown an increase in MDA concentration in erythrocytes by about 91%, which seems to have resulted from reduced activity of GPx and the lack of increase in activity of GR in blood red cells.     

Changes in fatty acid composition of lipids from birds, rodents, and preschool children exposed to lead

Chronic treatment with inorganic lead (Pb) has been shown to increase the proportion of arachidonic acid (ArA), as well as the arachidonate/linoleate (ArA/LA) ratio, in the fatty acids of lipids from a variety of avian tissues. Changes in two fatty acid-mediated phenomena, peroxidation of membrane lipids and synthesis of eicosanoid cytokines, are associated with this enhanced ArA content. The authors are not aware of any reports in the literature in which these effects of Pb have been described for any animals other than birds. In the current study, the authors investigated the effect of Pb on lipid metabolism in three species: avian, rodent, and human. The group of children identified as suffering environmental Pb exposure were from a Pb-surveillance program and had blood Pb concentrations (PbB) averaging 23 μg/dL. Turkey poults fed 100 ppm dietary Pb as Pb acetate-trihydrate for 19 d had a PbB of 46 μg/dL. Gastric intubation of rats with 80 mg Pb/kg/d for 10 d resulted in a PbB of 74 μg/dL. We analyzed fatty acid composition of whole blood from children, poults, and virgin rats. Low-dose (nongrowth inhibitory) Pb exposure resulted in significantly increased ArA concentration and ArA/LA ratio in blood from all species. Also analyzed were plasma and liver of poults, virgin rats, and pregnant rats and their fetuses. In plasma and liver from Pb-treated poults and virgin rats, ArA and the ArA/LA ratio were again enhanced. Pb intoxication also affected ω3 composition, increasing the concentrations of all long-chain ω3 fatty acids of fetuses from Pb-treated pregnant dams. The authors propose that altered fatty acid metabolism may be responsible for some indications of Pb poisoning. Possible consequences mediated through lipid peroxidation and production of ArA-derivative eicosanoids are considered.     

The influence of bisnaphthalimidopropyl polyamines on DNA instability and repair in Caco-2 colon epithelial cells

Bisnaphthalimido compounds bis-intercalate to DNA via the major groove and are potentially potent cancer therapeutics. Previously, we incorporated natural polyamines as linkers connecting the two naphthalimido ring moieties to create a series of soluble bisnaphthalimidopropyl polyamines (BNIPPs). Here, extending earlier work on bisnaphthalimidopropylspermidine (BNIPSpd)-induced apoptosis in colon adenocarcinoma Caco-2 cells, we compare the cytotoxicity and genotoxicity of BNIPSpd relative to the spermine and oxaspermine derivatives, bisnaphthalimidopropylspermine (BNIPSpm) and bisnaphthalimidopropyloxaspermine (BNIPOSpm). The order of cytotoxicity after 24 h was BNIPSpd (IC₅₀ = 0.47 μM) > BNIPSpm (IC₅₀ = 10.04 μM) > BNIPOSpm (IC₅₀ >50 μM). After a 72-h BNIPOSpm exposure, an IC₅₀ = 10.25 μM was achieved. With 4-h exposure to BNIPSpd or BNIPSpm or 12-h exposure to BNIPOSpm, concentrations ≥1 μM induced a significant dose-dependent increase in DNA damage as measured by alkaline single-cell gel electrophoresis. The longer incubation times required for BNIPOSpm to induce DNA strand breaks reflect a slower rate of BNIPOSpm cellular distribution as monitored via BNIPP fluorescence within the cells. Moreover, exposure to a non-genotoxic concentration of BNIPSpd, BNIPSpm (0.1 μM for 4 h) or BNIPOSpm (0.1 μM for 12 h) induced a significant decrease in repair of oxidative DNA damage induced by hydrogen peroxide. In conclusion, BNIPP exposure in Caco-2 cells is associated with significant induction of DNA damage and inhibition of DNA repair at non-genotoxic concentrations. The latter is a novel consequence of BNIPP–cell interactions which adds to the spectrum of therapeutically relevant activities that may be exploited for the design and development of naphthalimide-based therapeutics.     

Danthron Induces DNA Damage and Inhibits DNA Repair Gene Expressions in GBM 8401 Human Brain Glioblastoma Multiforms Cells

Our primary studies had shown that danthron induced cytotoxic effects, including apoptosis and inhibition of migration and invasion. However, danthron-affected DNA damage and repair gene expressions are not clear. In this study, we investigated to examine whether or not danthron induced DNA damage and inhibited DNA repair gene expression in human brain glioblastoma multiforms (GBM 8401) cells. The results from Comet assay indicated that incubation of GBM 8401 cells with 0, 50, 100 and 150 μM of danthron led to a longer DNA migration smear based on the single cell electrophoresis (Comet tail). The results from real-time PCR assay demonstrated that 100 μM of danthron for 24 h treatment in GBM 8401 cells led to decrease all examined ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR), breast cancer 1, early onset (BRCA-1), 14-3-3 proteins sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK) and O ⁶ -methylguanine-DNA methyltransferase (MGMT) mRNA expressions. Taken together, the present study showed that danthron caused DNA damage and inhibited DNA repair genes, which may be the factors for danthron-inhibited cell growth in vitro.     

Dietary arsenic affects dimethylhydrazine-induced aberrant crypt formation and hepatic global DNA methylation and DNA methyltransferase activity in rats

Cell culture studies have suggested that arsenic exposure results in decreased S-adenosylmethionine (SAM), causing DNA hypomethylation. Previously, we have shown that hepatic SAM is decreased and/or S-adenosylhomocysteine increased in arsenic-deprived rats; these rats tended to have hypomethylated DNA. To determine, the effect of dietary arsenic on dimethylhydrazine (DMH)-induced aberrant crypt formation in the colon, Fisher 344 weanling male rats were fed diets containing 0,05, or 50 μg As (as NaAsO₂)/g. After 12 wk, dietary arsenic affected the number of aberrant crypts (p<0.02) and aberrant crypt foci (p<0.007) in the colon and the amount of global DNA methylation (p<0.04) and activity of DNA methyltransferase (DNMT) (p<0.003) in the liver. In each case, there were more aberrant crypts and aberrant crypt foci, a relative DNA hypomethylation, and increased activity of DNMT in the rats fed 50 μg As/g compared to those fed 0.5 μg As/g. The same phenomenon, an increased number of aberrant crypts and aberrant crypt foci, DNA hypomethylation, and increased DNMT tended to hold when comparing rats fed the diet containing no supplemental arsenic compared to rats fed 0.5 μg As/g. The data suggest that there is a threshold for As toxicity and that possibly too little dietary As could also be detrimental. The U.S. Department of Agriculture, Agricultural Research Service. Northern Plains Area is an equal opportunity/affirmative action employer and all agency services are available without discrimination.     

The role of reactive oxygen species in silicon dioxide nanoparticle-induced cytotoxicity and DNA damage in HaCaT cells

The increasing applications of silicon dioxide (SiO₂) nanomaterials have been widely concerned over their biological effects and potential hazard to human health. In this study, we explored the effects of SiO₂ nanoparticles (15, 30, and 100 nm) and their micro-sized counterpart on cultured human epidermal Keratinocyte (HaCaT) cells. Cell viability, cell morphology, reactive oxygen species (ROS), DNA damage (8-OHdG, γH2AX and comet assay) and apoptosis were assessed under control and SiO₂ nanoparticles exposed conditions. As observed in the Cell Counting Kit-8 (CCK-8) assay, exposure to 15, 30 or 100 nm SiO₂ nanoparticles at dosage levels between 0 and 100 μg/ml decreased cell viability in a concentration- and size dependent manner and the IC50 of 24 hour exposure was 19.4 ± 1.3, 27.7 ± 1.5 and 35.9 ± 1.6 μg/ml for 15, 30 and 100 nm SiO₂ nanoparticles, respectively. Morphological examination revealed cell shrinkage and cell wall missing after SiO₂ nanoparticle exposure. Increase in intracellular ROS level and DNA damage as well as apoptosis were also observed in SiO₂ nanoparticle-exposed HaCaT cells. Exposure to SiO₂ nanoparticles results in a concentration- and size-dependent cytotoxicity and DNA damage in cultural HaCaT cells which is closely correlated to increased oxidative stress.     

Adult:Child Differences in the Intraspecies Uncertainty Factor: A Case Study Using Lead

Adults and children differ in their susceptibility to the toxic effects of lead. Lead was therefore used as a case study to evaluate intraspecies differences by comparing the adult and child minimal Lowest Observed Adverse Effect Level (LOAEL) or the No Observed Adverse Effect Level (NOAEL), allowing an evaluation of the ten-fold intraspecies uncertainty factor (UF). The lead intakes (in µg/kg/d) necessary to achieve target blood lead (PbB) levels reflecting the minimal LOAEL or NOAEL were determined using biokinetic slope factors (BKSFs), which relate lead uptake to PbB levels. The analyses assumed chronic, low-level oral exposure to lead, and the response of a typical adult and child. Child analyses used a target geometric mean (GM) PbB of 4.6?µg/dL (95% of population <10?µg/dL), resulting in lead intakes of 1.9?µg/kg/day (assuming 100% soluble lead) and 4.9?µg/kg/day (assuming 25% soluble lead and 75 % soil lead). Adult analyses assumed intake of 100 % soluble lead, and used target GM PbB levels of 4.2?µg/dL (95% of population <11.1 µg/dL) and 11.4?µg/dL (95% of population <30?µg/dL), resulting in lead intakes of 1.9?µg/kg/day and 5.1?µg/kg/day, respectively. The results indicate that despite the greater vulnerability of young children to the effects of lead as compared to adults, the minimal LOAEL or NOAEL for lead is remarkably similar between children and adults. In this case, the application of a tenfold intraspecies uncertainty factor to adjust the adult minimal LOAEL or NOAEL for a child would be unnecessary, despite the well-established vulnerability of children to lead.     

Monitoring Metals in Blood and Hair of the Population Living Near a Hazardous Waste Incinerator: Temporal Trend

The concentrations of As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sn, Tl, and V were determined in hair of 96 school children and in blood of 144 adults living in the vicinity of a hazardous waste incinerator (HWI) (Constantí, Tarragona County, Catalonia, NE Spain). The results were compared with those obtained in previous (1998 and 2002) surveys performed in the same area. Data were analyzed in terms of age, sex, and specific place of residence. Current mean concentrations in hair ranged between not detected (ND) (As, Be, and Tl) and 1.31 μg/g for Cr. In blood, Be, Hg, Mn, Sn, and Tl levels were under the respective detection limits. The mean blood concentrations of the remaining elements ranged from 0.34 μg/dL for Cd, to 2.40 μg/dL for Pb. Significant differences in hair and blood in relation to gender were only noted for Pb in blood. In general terms, metal concentrations in hair and blood from subjects living in Tarragona County are lower than most levels reported for other countries in recent years.     

Influence of Plasmid Concentration on DNA Electrotransfer In Vitro Using High-Voltage and Low-Voltage Pulses

DNA electrotransfer in vivo for gene therapy is a promising method. For further clinical developments, the efficiency of the method should be increased. It has been shown previously that high efficiency of gene electrotransfer in vivo can be achieved using high-voltage (HV) and low-voltage (LV) pulses. In this study we evaluated whether HV and LV pulses could be optimized in vitro for efficient DNA electrotransfer. Experiments were performed using Chinese hamster ovary (CHO) cells. To evaluate the efficiency of DNA electrotransfer, two different plasmids coding for GFP and luciferase were used. For DNA electrotransfer experiments 50 μl of CHO cell suspension containing 100, 10 or 1 μg/ml of the plasmid were placed between plate electrodes and subjected to various combinations of HV and LV pulses. The results showed that at 100 μg/ml plasmid concentration LV pulse delivered after HV pulse increased neither the percentage of transfected cells nor the total transfection efficiency (luciferase activity). The contribution of the LV pulse was evident only at reduced concentration (10 and 1 μg/ml) of the plasmid. In comparison to HV (1,200 V/cm, 100 μs) pulse, addition of LV (100 V/cm, 100 ms) pulse increased transfection efficiency severalfold at 10 μg/ml and fivefold at 1 μg/ml. At 10 μg/ml concentration of plasmid, application of four LV pulses after HV pulse increased transfection efficiency by almost 10-fold. Thus, these results show that contribution of electrophoretic forces to DNA electrotransfer can be investigated in vitro using HV and LV pulses.     

An Epidemiological Survey of Blood Lead Level in Tibetan Youth 10–18 Years Old in Songpan,China

There are few studies on Tibetan youth’s blood lead level (BLL) and environmental pollution in China. The objective of this project was to conduct a preliminary investigation on the blood lead level of Tibetan youth. Chinese Han youth’s BLL was also investigated as a control group. A total of 846 Tibetan youth and 785 Han youth were tested for BLL from September to October in 2007. Both of the mean BLL (6.4 μg/dL) and the frequency of high BLL (≥10 μg/dL) of Tibetan youth (7.7%, 65 of 846) were lower than those of Han youth (6.7 μg/dL; 13.2%, 104 of 785). But they are still higher compared with the BLL of youth in developed countries (1.1 μg/dL; USA 2005 census). The BLL of boys was significantly higher than that of girls, both in Tibetan and Han youth (p = 0.033 and p = 0.000, respectively). The study shows that Chinese Han and Tibetan youth's lead poisoning prevention and treatment lags far behind developed countries. These findings have implications for environmental health policy.     

Evaluation of Association between Biomarkers of Lead Exposure in Sardinian Children (Italy)

The aim of this work is to verify whether there are statistically significant correlations between the concentrations of lead in blood, urine, and hair in children. The sample collected in 2007 consists of 163 children of both sexes from 11–14-year-olds, living in three municipalities of Sardinia (Italy). Inductively coupled plasma atomic mass spectrometry has been used in the determination of lead concentration in biological material. For the overall sample, there is a non-significant partial correlation among the three matrices. However, for subjects with blood lead levels ≥5 μg/dL, there is a significant positive partial correlation between the lead levels in blood and hair, but not between blood and urine or between urine and hair. The results suggest that blood is the preferred biomarker to ascertain lead exposure in human populations, whereas hair can be used as a tool screening when an area is exposed to medium or high lead pollution.     

Midvale Community Lead Study

Abstract

The primary objective of this study was to ascertain whether children living in close proximity to mill tailings and a former lead smelter site were currently exhibiting elevated blood lead (PbB) concentrations. To address this issue, the mean PbB for community children and the relationship between PbB and the proximity of the child's residence to the site was estimated. A secondary objective was to identify and quantify accessible lead (Pb) and arsenic (As) in the environment (e.g. Pb in soil, dust, paint and water or As in soil and dust). A third objective was to test for association between specific sources of environmental Pb and PbB and to estimate the relative contribution of these proximate sources of lead to the children's PbB. The data analytic methods allowed estimation of both direct and indirect impact of environmentally accessible Pb. The average PbB level of all children screened in Midvale was 5.2 μg dL^?1. Three percent exceeded 15 μg dL^?1; 12.7% exceeded 10 μg dL^?1. Pb-based house paint and Pb contaminated soil were identified as principal contributors to PbB. PbB was found to increase 1.25 μg dL^?1 per 1,000 ppm increase in lead in soil. Proximity of residence to the mill and smelter site was found to be a strong predictor of Pb in soil, and therefore indirectly related to increases in PbB.     

Effects of radiation quality on interactions between oxidative stress, protein and DNA damage in Deinococcus radiodurans

Ionizing radiation damages DNA and also induces oxidative stress, which can affect the function of proteins involved in DNA repair, thereby causing repair of DNA damage to become less efficient. We previously developed a mathematical model of this potentially synergistic relationship and applied it to γ-ray exposure data on the radiation-resistant prokaryote Deinococcus radiodurans. Here, we investigate the effects of radiation quality on these processes by applying the model to data on exposures of D. radiodurans to heavy ions with linear energy transfer (LET) of 18.5–11,300 keV/μm. The model adequately describes these data using three parameters combinations: radiogenic DNA damage induction, repair protein inactivation and cellular repair capacity. Although statistical uncertainties around best-fit parameter estimates are substantial, the behaviors of model parameters are consistent with current knowledge of LET effects: inactivation cross-sections for both DNA and proteins increase with increasing LET; DNA damage yield per unit of radiation dose also increases with LET; protein damage per unit dose tends to decrease with LET; DNA and especially protein damage yields are reduced when cells are irradiated in the dry state. These results suggest that synergism between oxidative stress and DNA damage may play an important role not only during γ-ray exposure, but during high-LET radiation exposure as well.     

Estimation of Dietary Pb and Cd Intake from Pb and Cd in Blood or Urine

Successful trials were made to estimate the dietary daily intake of lead (Pb) and cadmium (Cd) via foods from the levels of the metals in blood or urine. In practice, 14 and 15 reports were available for Pb and Cd in blood (Pb-B and Cd-B), urine (Pb-U and Cd-U) and 24-h diet duplicates (Pb-D and Cd-D), respectively, from which 68 pairs each of Pb or Cd in blood and food duplicates [each being geometric mean (GM) values for the survey sites] were obtained. Regression analysis revealed that there was a significant correlation between Pb-B and Pb-D, and also between Cd-B and Cd-D, suggesting that it should be possible to estimate both Pb-D and Cd-D from Pb-B and Cd-B, respectively. For Cd-U, the number of available cases was limited (20 pairs), but a significant correlation was detected between Cd-U (as Cd-U_cr, or Cd levels in urine as corrected for creatinine concentration) and Cd-D. Care should be taken in estimating Pb-D from Pb-B, as the ratio of Pb-D over Pb-B may decrease as a function of increasing Pb-B levels. The Pb-D (μg/day) for typical Japanese women with Pb-B of 15 μg/l was best estimated to be 13.5 μg/day. No Cd-B- or Cd-U_cr-dependent change was detected in case of Cd. The best estimate of Cd-D for Cd-B at 1.5 μg/l should be about 19.4 μg/day.     

DNA damage in mouse lymphocytes exposed to curcumin and copper

Dietary polyphenolics, such as curcumin, have shown antioxidant and anti-inflammatory effects. Some antioxidants cause DNA strand breaks in excess of transition metal ions, such as copper. The aim of this study was to evaluate thein vitro effect of curcumin in the presence of increasing concentrations of copper to induce DNA damage in murine leukocytes by the comet assay. Balb-C mouse lymphocytes were exposed to 50 μM curcumin and various concentrations of copper (10 μM, 100 μM and 200 μM). Cellular DNA damage was detected by means of the alkaline comet assay. Our results show that 50 μM curcumin in the presence of 100–200 μM copper induced DNA damage in murine lymphocytes. Curcumin did not inhibit the oxidative DNA damage caused by 50 μM H₂O₂ in mouse lymphocytes. Moreover, 50 μM curcumin alone was capable of inducing DNA strand breaks under the tested conditions. The increased DNA damage by 50 μM curcumin was observed in the presence of various concentrations of copper, as detected by the alkaline comet assay.     

Lead Dysregulates Serine/Threonine Protein Phosphatases in Human Neurons

It is well established that lead (Pb) exposure in humans leads to learning and memory impairment. However, the biological and molecular mechanisms are still not clearly understood. When over activated, serine/threonine protein phosphatases are known to function as a constraint on learning and memory. Activation of these phosphatases can also result in cytoskeletal changes that will adversely affect learning and memory. We investigated the effects of Pb exposure on these phosphatases in primary cultures of human neurons. Neurons were exposed to physiologically relevant concentrations of Pb (5, 10, 20 and 40 μg/dL) and total phosphatase and PP2A activities were determined in neuronal lysate using para-nitrophenyl phosphate (pNPP), and a PP2A-specific phosphopeptide as substrates. Expression of various serine/threonine phosphatases, tau and its phosphorylation state were determined by Western blot (WB) and immunocytochemistry (ICC). We found that the total phosphatase activity in the neuronal lysate was increased by 30–50% by all the concentrations of Pb tested. PP2A activity was increased by 5 μg/dL Pb only. PP1 expression was increased (ranging from 25–50%) by 10, 20 and 40 μg/dL of Pb. PP2B expression was increased substantially (up to 2.5-fold) by 10 μg/dL Pb, whereas, higher concentrations did not show any effect. On the other hand, Pb (at all concentrations used) decreased expression of PP2A and PP5. Pb exposure induced substantial hyperphosphorylation of tau at serine 199/202 by 5 and 10 μg/dL Pb, and Threonine 231 at higher doses. Expression of total tau was mostly unaffected by lead. Immunocytochemistry data confirmed the WB results of expression of PP1, PP2A, tau protein and the phosphorylation of tau. These results support our hypothesis that Pb exposure up regulates some of the serine/threonine phosphatases (PP1 and PP2B) that are known to impair memory formation, and suggest a novel mechanism of Pb neurotoxicity.     

Monitoring of mycotoxin biomarkers in the Czech Republic

AFM₁ was determined in 72 (72%) samples of human urine, range 19-6064 pg/g creatinine, mean 367 pg/g creatinine, median 158 pg/g creatinine and 90% percentile 755 pg/g creatinine in 1997. AFM₁ was determined in 46 (43.8%) samples of human urine, range 21-19219 pg/g creatinine, mean 414 pg/g creatinine, median 96 pg/g creatinine and 90% percentile 415 pg/g creatinine in 1998. OTA was determined in 2077 (94.2%) samples of human serum, range 0.1–13.7 μg/L, mean 0.28 μg/L, median 0.2 μg/L and 90% percentile 0.5 μg/L in 1994–2002. OTA was determined in 12 (40%) samples of human kidneys, range 0.1–0.2 μg/kg, mean 0.07 μg/kg, and median 0.05 μg/kg in 2001. Presented at the 26^th Mykotoxin-Workshop in Herrsching, Germany, May 17–19, 2004.     

Alkylation-induced genotoxicity as a predictor of DNA repair deficiency following experimental oral carcinogenesis

The aim of this study was to evaluate alkylation induced genotoxicity as a result of DNA repair deficiency during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis by means of single cell gel (comet) assay. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. Blood samples and oral mucosa cells collected from all animals were divided into two aliquots of 20 μL each to study basal DNA damage and DNA damage due to genotoxin sensitivity. The first aliquot was processed immediately for comet assay to assess basal DNA damage. The second aliquot was treated with a known genotoxin, methylmetanesulfonate. Significantly greater DNA damage was noticed to oral mucosa cells from 4, and 12 weeks post-treatment. Peripheral blood cells did show statistically significant differences (P < 0.05) after 20 weeks-group (squamous cell carcinoma). In conclusion, alkylation induced genotoxicity as a result of DNA repair deficiency is present in oral mucosa cells following oral experimental carcinogenesis.     

Evaluation of increased proportion of cells with unusually high sister chromatid exchange counts as a cytogenetic biomarker for lead exposure

Sister chromatid exchange (SCE) frequency and high-frequency cells (HFCs) were analyzed in 50 storage battery plant workers with mean blood lead level (BLL) of 40.14±9.99 μg/dL. The mean BLL in the control group (n=30) was 9.77±1.67 μg/dL. This difference in mean BLLs between control and exposed group was statistically significant (p<0.05) and reflects clearly the lead exposure in the workers. Urinary aminolevulinic acid (U-ALA) was also determined in both control (3.37±0.89 mg ALA/g creatinine) and exposed groups (12.39±6.18 mg ALA/g creatinine) and U-ALA excretion was statistically higher (p<0.05) in lead-exposed workers. The relationship between biomarkers of lead exposure/effect and HFC percentage was higher than the relationship between biomarkers of lead exposure/effect and SCE frequency. Accordingly, HFC analysis seemed to be more sensitive than the SCE analysis as a cytogenetic biomarker for lead exposure. Additionally, the statistically significant correlation (r ²=0.880, p<0.01) between U-ALA excretion and HFC percentage in lead-exposed workers supported the probability of ALA mediated indirect mechanism for lead genotoxicity.