Evaluation of low-to-moderate arsenic exposure, metabolism and skin lesions in a Turkish rural population exposed through drinking water.

BACKGROUND: There is no human data regarding the exposure, metabolism and potential health effects of arsenic (As) contamination in drinking water in the Central Anatolian region of Turkey. METHODS: Residents in ten villages with drinking water of total As (T-As) level >50 µg L-1 and 10-50 µg L-1 were selected as an exposed group (n = 420) and <10 µg L-1 as an unexposed group (n = 185). Time-weighted average-As (TWA-As) intake was calculated from T-As analysis of drinking water samples. Concentrations of T-As in urine and hair samples, urinary As species [i.e., As(III), As(V), MMA(V) and DMA(V], and some micronutrients in serum samples of residents of the study area were determined. Primary and secondary methylation indices (PMI and SMI, respectively) were assessed from urinary As species concentrations and the presence of skin lesion was examined. RESULTS: TWA-As intake was found as 75 µg L-1 in the exposed group. Urinary and hair T-As and urinary As species concentrations were significantly higher in the exposed group (P < 0.05). The PMI and SMI values revealed that methylation capacities of the residents were efficient and that there was no saturation in As metabolism. No significant increase was observed in the frequency of skin lesions (hyperpigmentation, hypopigmentation, keratosis) of the exposed group (P > 0.05). Only frequency of keratosis either at the hand or foot was higher in individuals with hair As concentration >1 µg g-1 (P < 0.05). CONCLUSIONS: Individuals living in the study area were chronically exposed to low-to-moderate As due to geological contamination in drinking water. No significant increase was observed in the frequency of skin lesions. Because of the controversy surrounding the health risks of low-to-moderate As exposure, it is critical to initiate long-term follow-up studies on health effects in this region.

Associations of persistent organic pollutants in human adipose tissue with retinoid levels and their relevance to the redox microenvironment.

Humans are exposed to a myriad of chemical substances in both occupational and environmental settings. Persistent organic pollutants (POPs) have drawn attention for their adverse effects including cancer and endocrine disruption. Herein, the objectives were 1) to describe serum and adipose tissue retinol levels, along with serum retinol binding protein 4 (RBP4) concentrations, and 2) to assess the associations of adipose tissue POP levels with these retinoid parameters, as well as their potential interaction with the previously-observed POP-related disruption of redox microenvironment. Retinol was measured in both serum and adipose tissue along with RBP4 levels in serum samples of 236 participants of the GraMo adult cohort. Associations were explored by multivariable linear regression analyses and Weighted Quantile Sum regression. Polychlorinated biphenyls (PCBs) 180, 153 and 138 were related to decreased adipose tissue retinol levels and increased serum RBP4/retinol ratio. Dicofol concentrations > limit of detection were associated with decreased retinol levels in serum and adipose tissue. Additionally, increased adipose tissue retinol levels were linked to an attenuation in previously-reported associations of adipose tissue PCB-153 with in situ superoxide dismutase activity. Our results revealed a suggestive link between retinoids, PCBs and redox microenvironment, potentially relevant for both mechanistic and public health purposes.

Exposure to particulate matter: a brief review with a focus on cardiovascular effects, children, and research conducted in Turkey.

Exposure to environmental particulate matter (PM), outdoor air pollution in particular, has long been associated with adverse health effects. Today, PM has widely been accepted as a systemic toxicant showing adverse effects beyond the lungs. There are numerous studies, from those in vitro to epidemiological ones, suggesting various direct and indirect PM toxicity mechanisms associated with cardiovascular risks, including inflammatory responses, oxidative stress, changes in blood pressure, autonomic regulation of heart rate, suppression of endothelium-dependent vasodilation, thrombogenesis, myocardial infarction, and fibrinolysis. In addition to these and other health risks, considerations about air quality standards should include individual differences, lifestyle, and vulnerable populations such as children. Urban air pollution has been a major environmental issue for Turkey, and this review will also address current situation, research, and measures taken in our country.

Investigation of spatial and temporal variation of particulate matter in vitro genotoxicity and cytotoxicity in relation to the elemental composition.

Even though the outdoor air pollution and its major component Particulate Matter (PM) are recently classified as human carcinogen, attempts to elucidate the underlying mechanisms of PM toxicity are still crucial and continuing with in vitro approaches in various environmental circumstances. Present study investigated the genotoxicity (Comet assay) and the cytotoxicity (lactate dehydrogenase (LDH) leakage and the water-soluble tetrazolium (WST-1) assays) of 30 daily PM2.5 samples collected in the Kütahya province, to address their daily variability in effects with season (i.e. winter versus summer) and location (i.e. rural versus urban) using A549 human lung cancer epithelial cell line, as well as in relation to their chemical composition, specifically trace elements, organic carbon (OC) and elemental carbon (EC). The genotoxicity, measured by the percentage tail intensity (TI), of the daily PM2.5 samples at the traffic dense urban station was higher than that of the rural site for 80% of the parallel days. The genotoxicity was significant in the winter at the urban and in the summer at the rural site. Cytotoxicity was the highest for the winter urban samples. The PM2.5 mass, OC, and EC concentrations were not correlated to DNA damage, while there were correlations with Mn, Fe, Cu and Ba at the rural PM2.5 samples, and Mn, Co and Ni at the urban samples, respectively. The present study is confirming that the complex composition of PM2.5 originating from spatial and temporal changes can cause differences in the health effects.

Corrosion potential in artificial saliva and possible genotoxic and cytotoxic damage in buccal epithelial cells of patients who underwent Ni-Cr based porcelain-fused-to-metal fixed dental prostheses.

Nickel-chromium(Ni-Cr) based alloys account for the majority of the porcelain-fused-to-metal fixed dental prostheses(PFM-FDPs) on account of their superior properties despite both nickel and chromium being known as human carcinogens. Understanding the genotoxicity and the cytotoxicity alongside the characteristics of corrosion behavior of the alloy is vital for understanding their biocompatibility. This study has evaluated whether the Ni-Cr based alloys corroded in artificial saliva by analyzing alloy decomposition at different pH levels and immersion durations(7, 14, 21, and 28 days) using inductively coupled plasma-optic emission spectrophotometry(ICP-OES). The principal aim of the study was to determine the possible genotoxicity and cytotoxicity using micronucleus(MN) and other nuclear anomaly frequencies [nuclear bud(NBUD), binucleated(BNC), condensed chromatin(CC), karyorrhectic(KhC), pyknotic(PC) and karyolytic(KC) cells] and various cytome parameters [basal cells(BC), differentiated cells(DF)] with the buccal epithelial cell(BEC) micronucleus cytome assay(BMCyt). This test was administered at 1 pre- and 3 post-treatment time points to 40 patients who underwent installation of PFM-FDPs made of Ni-Cr based alloy. Furthermore, at the final post-treatment time point, saliva cotinine levels were measured with salivary cotinine quantitative enzyme immunoassay(EIA) kit and information obtained by questionnaire prior to the first pre-treatment time point was confirmed. The highest greatest release of Ni and Cr ions were seen at pH 2.3. MN and micronucleated cell frequencies, and BNC cell frequencies were significantly elevated at post-treatment time points(p < 0.03). BC, CC, KhC, PC and KC cell frequencies however were not significantly different between pre-and post-treatment time points(p > 0.05). MN frequency was significantly lower in non-smokers than in current and former smokers(p < 0.001) at the pre-treatment time point. There was no significant correlation between the unit number of PFM-FDPs and MN frequencies. Our results revealed that Ni-Cr based alloys are prone to corrosion and that PFM-FDPs fabricated with Ni-Cr based alloys may induce genotoxic effects rather than cytotoxic effect.

Formation of PAH-DNA adducts after in vivo and vitro exposure of rats and lung cells to different commercial carbon blacks.

OBJECTIVE: The current study was designed to test the possible release and bioavailability of polycyclic aromatic hydrocarbons (PAHs) from a set of commercial carbon blacks (CBs) as well as the ability of these PAHs to form bulky DNA adducts. METHODS: In four commercial CBs (Printex 90, Sterling V, N330, Lampblack 101), leaching of PAH was examined through (1) release of parent PAHs in saline with or without surfactant, and (2) PAH adducts in lung epithelial cells (A549) or in rat lungs after exposure to two CBs (Printex 90, Sterling V) for 13 weeks (50 mg/m(3)). In vitro experiments were done with original and extracted particles, as well as organic extracts of CB in DMSO. As positive controls, B[a]P (0.03 microM) and a mixture of 16 PAHs (0.1 microM) were used. RESULTS: No leaching of PAHs was measured in saline or surfactant-containing saline. In vitro incubations with CB particles (30-300 microg/cm(2)) revealed no adduct spots except for Sterling V. However, the spot was not concentration dependent and remains unidentified. Lung DNA from rats after inhalation of Printex 90 or Sterling V showed no spots related to PAH-DNA adduct formation compared to sham-exposed rats. CONCLUSION: The results suggest that PAHs are very tightly bound to these CBs. Only using organic extracts or particles of low-surface Sterling V, with high PAH content, PAHs may become available to form PAH-DNA adducts. However, the in vitro conditions showing this effect will not be encountered in vivo and renders this mechanism in particle-induced lung cancer at in vivo exposures highly unlikely.

In vitro genotoxicity assessment of commercial quartz flours in comparison to standard DQ12 quartz.

Crystalline silica has been classified as a human carcinogen, but there is still considerable debate on its variable fibrogenic and carcinogenic potential. We investigated genotoxicity of a panel of four quartz flours in comparison to DQ12 standard quartz with similar size and surface area, using single cell gel electrophoresis (SCGE) or comet assay. A549 human lung epithelial cells were incubated for 4 hours with different concentrations of quartz ranging from 1.6 to 200 micrograms/cm2 and cytotoxicity was assessed using leakage of lactate dehydrogenase (LDH), trypan blue exclusion and conversion of a metabolic substrate (MTT). DNA strand breakages were seen with all quartzes at an in vitro concentration of 200 micrograms/cm2. At this concentration all tests and quartz samples showed significant cytotoxicity. The most toxic quartz flour (Qz 2/1-C) but not DQ12, showed an increase in strand breaks at 40 micrograms/cm2 in cell culture. At this concentration no cytotoxicity was seen with LDH and MTT, but a significant increase in cells with trypan blue uptake was noted. No differences in tail moment percentage were observed at equal concentrations of different quartz flours. Also no correlation between DNA damage and OH-radical generation or surface radicals as measured by electron spin resonance was observed. We conclude that quartzes do not cause strand breaks without concomitant cell toxicity and a sufficient in vitro concentration of > 40 micrograms/cm2 can only be reached in vivo with instillation of massive doses (> 100 mg). Therefore, in vitro genotoxicity found here is unlikely to explain the genotoxicity observed in in vivo studies with the same and other quartzes.

Cytogenetic analysis of buccal cells from shoe-workers and pathology and anatomy laboratory workers exposed to n-hexane, toluene, methyl ethyl ketone and formaldehyde.

People employed in the shoe manufacture and repair industry are at an increased risk for cancer, the strongest evidence being for nasal cancer and leukaemia. A possible causal role for formaldehyde is likely for cancer of the buccal cavity and nasopharynx. Exfoliated buccal cells are good source of tissue for monitoring human exposure to inhaled and ingested occupational and environmental genotoxicants. To assess the cytogenetic damage related to occupational exposure to airborne chemicals during shoe-making and the processes in pathology and anatomy laboratories, the micronuclei (MN) count per 3000 cells was measured in buccal smears from shoe-workers (group I, n = 22) exposed to mainly n-hexane, toluene and methyl ethyl ketone (MEK) and from anatomy and pathology staff (group II, n = 28) exposed to formaldehyde (FA). Eighteen male university staff were used as controls. The mean time-weighted average (TWA) concentrations of n-hexane, toluene and MEK in 10 small shoe workshops were 58.07 p.p.m., 26.62 p.p.m. and 11.39 p.p.m., respectively. The measured air concentrations of FA in the breathing zone of the anatomy and pathology laboratory workers were between 2 and 4 p.p.m. Levels of 2,5-hexadione (2,5-HD) and hippuric acid (HA), metabolic markers of n-hexane and toluene exposure, respectively, were significantly higher in the urine of workers in group I than in control subjects (p < 0.001 and p < 0.01, respectively). The mean (+/- SD) MN (0/00) [corrected] frequencies in buccal mucosa cells from workers in group I, group II and controls were 0.62 +/- 0.45%, 0.71 +/- 0.56% and 0.33 +/- 0.30%, respectively (p < 0.05 and p < 0.05 compared with controls for group I and group II, respectively). The effects of smoking, age and duration of exposure on the frequency of micronucleated buccal cells from workers in all three groups studied were also evaluated. Overall, the results suggest that occupational exposure to organic solvents, mainly n-hexane, toluene, MEK and FA, may cause cytogenetic damage in buccal cells and that use of exfoliated buccal cells seems to be appropriate to measure exposure to organic solvents.

Oxidant-induced DNA damage by quartz in alveolar epithelial cells.

Respirable quartz has recently been classified as a human carcinogen. Although, studies with quartz using naked DNA as a target suggest that formation of oxyradicals by particles may play a role in the DNA-damaging properties of quartz, it is not known whether this pathway is important for DNA damage in the target cells for quartz carcinogenesis, i.e. alveolar epithelial cells. Therefore, we determined in vitro DNA damage by DQ12 quartz particles in rat and human and alveolar epithelial cells (RLE, A549) using the single cell gel electrophoresis/comet assay. The radical generation capacity of quartz was analysed by electron spin resonance (ESR) and by immunocytochemical analysis of the hydroxyl radical-specific DNA lesion 8-hydroxydeoxyguanosine (8-OHdG) in the epithelial cells. Quartz particles as well as the positive control hydrogen peroxide, caused a dose-dependent increase in DNA strand breaks in both cell lines. DNA damage by quartz was significantly reduced in the presence of the hydroxyl-radical scavengers mannitol or DMSO. The involvement of hydroxyl radicals was further established by ESR measurements and was also demonstrated by the ability of the quartz to induce formation of 8-OHdG. In conclusion, our data show that quartz elicits DNA damage in rat and human alveolar epithelial cells and indicate that these effects are driven by hydroxyl radical-generating properties of the particles.