Low-dose hexavalent chromium(VI) exposure promotes prostate cancer cell proliferation by activating MAGEB2-AR signal pathway.

Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with several malignancies, such as lung cancer, but little information was available about the effects of its low-dose environmental exposure in prostate cancer. Our previous study has shown that low-dose Cr(VI) exposure could promote prostate cancer(PCa) cell growth in vitro and in vivo. In the present study, we furthermore found that low-dose Cr(VI) exposure could induce DNA demethylation in PCa cells. Based on our transcriptome sequencing data and DNA methylation database, we further identified MAGEB2 as a potential effector target that contributed to tumor-promoting effect of low-dose Cr(VI) exposure in PCa. In addition, we demonstrated that MAGEB2 was upregulated in PCa and its knockdown restrained PCa cell proliferation and tumor growth in vitro and in vivo. Moreover, Co-IP and point mutation experiments confirmed that MAGEB2 could bind to the NH2-terminal NTD domain of AR through the F-box in the MAGE homology domain, and then activated AR through up-regulating its downstream targets PSA and NX3.1. Together, low-dose Cr(VI) exposure can induce DNA demethylation in prostate cancer cells, and promote cell proliferation via activating MAGEB2-AR signaling pathway. Thus, inhibition of MAGEB2-AR signaling is a novel and promising strategy to reverse low-dose Cr(VI) exposure-induced prostate tumor progression, also as effective adjuvant therapy for AR signaling-dependent PCa.

Eriodictyol inhibits breast carcinogenesis by targeting circ_0007503 and repressing PI3K/Akt pathway.

BACKGROUND: Eriodictyol in citrus fruits, Eriodictyon californicum and several Chinese herbal medicines shows great promise for chronic disease prevention, including cancers. However, its role in chemopreventive activities against breast carcinogenesis is unknown. PURPOSE: In the present study, we investigated the chemopreventive effect and the underlying mechanism of eriodictyol on carcinogens-induced breast carcinogenesis in vivo and in vitro. METHODS: The carcinogenic transformation in MCF10A cells was induced by the environmental carcinogens in vitro. The chemopreventive effect in vivo was evaluated by using the experimental model of 1-methyl-1-nitrosourea (MNU)-induced mammary tumorigenesis in rats. The activation of the PI3K/Akt pathway was detected by western blot assay; the levels of circular RNAs (circRNAs) were measured by qRT-PCR. RESULTS: First, eriodictyol significantly reduces cells viability and induces apoptosis in breast cancer cells in a dose-dependent manner in vitro (P < 0.05). Next, eriodictyol could effectively suppress environmental carcinogens-induced acquisition of carcinogenic properties in human breast epithelial cell MCF10A (P < 0.05). In vivo, eriodictyol administration reduces the incidence of mammary tumor by 50% in carcinogen-treated female rats (P < 0.05). Further study revealed that eriodictyol represses the PI3K/Akt signaling pathway and down-regulates the level of circ_0007503 in breast cancer cells and in breast carcinogenesis (P < 0.01). When the effect of eriodictyol on circ_0007503 was blocked by transfection of a circ_0007503 over-expression plasmid, the cytotoxic effects and the suppression of the PI3K/Akt pathway of eriodictyol in breast cancer cells were significantly reduced (P < 0.05). CONCLUSION: Our data indicated that eriodictyol could effectively suppress breast carcinogenesis in vitro and in vivoThe mechanism may be attributed to targeting circ_0007503 and inhibiting PI3K/Akt pathway.

Chromium (III) and chromium (VI) as important players in the induction of genotoxicity - current view.

INTRODUCTION: Genotoxicity of chemical compounds is primarily associated with the interaction with DNA, formation of mutations, damage to chromosomes and initiating carcinogenesis processes. Currently, many compounds found in the environment are considered to be genotoxic agents, among them chromium: trivalent (III) and hexavalent (VI). The genotoxicity of hexavalent (VI) chromium has been proven in numerous epidemiological, in vitro and in vivo studies. The main source of Cr (VI) is environmental pollution associated with its use in various industries. On the other hand, the role of chromium (III) as a microelement is widely discussed. Due to its beneficial properties, associated with maintaining adequate blood glucose levels and supporting weight loss, it is widely used in the form of dietary supplements, often in doses exceeding the daily requirement. However, the safety of chromium compounds is disputable. Data about the mechanism of genotoxic effects are still incomplete. OBJECTIVE: The aim of this review is to present the current knowledge about the induction of genotoxicity from two forms of chromium: trivalent (III) and hexavalent (VI). STATE OF KNOWLEDGE: Chromium (VI) is a carcinogen with proven mutagenic and genotoxic effects, but this issue is still being investigated by scientists. In recent years, numerous studies have also been conducted on the genotoxic effect of chromium (III). CONCLUSIONS: Due to the still unexplained mechanism of the genotoxic action and incomplete knowledge about the transformation of chromium in the body, further research is needed, especially due to the growing popularity of Cr (III) compounds and their consumption in the form of dietary supplements and doubts as to the safety of its use, as well as environmental exposure to Cr (VI).

Mangiferin offers protection against deleterious effects of pharmaceuticals, heavy metals, and environmental chemicals.

Mangiferin (MGF) is a polyphenolic C-glucosyl-xanthone extracted from the mango tree (Mangifera indica). MGF has shown diverse effects such as antioxidant, antiapoptotic, radical scavenging, and chelating properties. MGF also has been shown to modulate inflammatory pathways. In this review, we examined and evaluated the literature dealing with the protective effects of MGF against various chemical toxicities. Our literature review indicated that the MGF-induced protective effects against the toxic effects of pharmaceuticals, heavy metals and environmental chemicals were mainly mediated via suppression of lipid peroxidation, oxidative stress (along with enhancement of the antioxidant enzyme), inflammatory factors (TNF-α, IL-6, IL-10, and IL-12), and activation of PI3K/Akt and the MAPK survival signaling pathway.

Dose estimation of radioactivity in groundwater of Srinagar City, Northwest Himalaya, employing fluorimetric and scintillation techniques.

The research is a maiden study aimed to assess the radioactivity in groundwater of Srinagar City using uranium and radon as proxies. In this study, 60 water samples were collected from various water sources that include bore wells, hand pumps and lakes of Srinagar City. Among them, 45 samples were taken from groundwater with depths ranging from 6 to - 126 m and the rest of the 15 samples were collected from surface sources like lakes, rivers and tap water. A gamma radiation survey of the area was carried out prior to collection of water samples, using a gamma radiation detector. A scintillation-based detector was utilized to measure radon, while as LED fluorimetry was employed to assess uranium in water samples. The average uranium concentration was found to be 2.63 µg L-1 with a maximum value of 15.28 µg L-1 which is less than the globally accepted permissible level of 30 µg L-1. 222Radon concentration varied from 0.2 to 38.5 Bq L-1 with an average value of 8.9 Bq L-1. The radon concentration in 19 groundwater samples (32% of total sites) exceeded the permissible limits of 11 Bq L-1 set by USEPA. This information could be of vital importance to health professionals in Kashmir who are researching on the incidence of lung cancers in the region given the fact that radon is the second leading cause of lung cancers after smoking worldwide.

Cadmium and lead in geophagic clay consumed in Southern Nigeria: health risk from such traditional nutraceutical.

Geophagy is a cultural behavior, based on the recurrent intentional eating of clay soil, that is raising increasing concern as it implies multidimensional (space, time) potential risk of serious adverse health effects. This study investigated the level of toxic metals (Cd and Pb) in 20 Nigerian geophagic clays intended for both local consumption and distribution to the West Africa market. After sampling in 4 open markets in southern Nigeria (Akwa Ibom, Abia, Rivers, Imo), samples were subjected to digestion, ashing and analysis. The Pb levels in all samples exceeded the WHO/FAO maximum permissible limit of 0.1 mg kg-1 whereas 16% exceeded the Cd limit of 0.3 mg kg-1. The estimated daily intake of Pb for all samples ranged from 0.0032-0.0286 mg kgbw-1 day-1 to 0.0024-0.0215 mg kgbw-1 day-1 for children and adults, respectively. The estimated daily intakes for Cd ranged from bdl (below detection limit)-0.0010 mg kgbw-1 day-1 to bdl-0.0028 mg kgbw-1 day-1 for children and adults, respectively. In both cases, the WHO/FAO provisional Tolerable Weekly Intake is exceeded through the ingestion of these soils. Our results confirm health risks related to the geophagic practices, its role in exceeding health guidelines when considering aggregate exposure in the Nigerian scenario and body burden in developing organisms, young women, women at fertile age, and pregnant women. We discuss how geophagists consider clays as traditional nutraceuticals and how clarifying the nutraceutical role of geophagy could facilitate risk communication. Geophagic products are implicitly or explicitly marketed as dietary supplements, and as such they should be regulated (1) by labeling, and prohibition of scientifically unfounded health claims and (2) by safety standards before marketing. This is particularly critical when clays originate from countries living rapid, unplanned and uncontrolled development and dumped, like Nigeria.

Treating the Disease, Not the Symptom: Beyond NSAIDs.

Mitigating inflammation is clearly important in cancer prevention and control. Traditionally, pharmaceuticals have taken the lead in this problem. In an attempt to 'head them off at the pass', this Forum takes a hard look at the concept of 'better living through chemicals' and limiting proinflammatory chemicals entering the body.

Flower-like gold nanoparticles-based immunochromatographic test strip for rapid simultaneous detection of fumonisin B1 and deoxynivalenol in Chinese traditional medicine.

A flower-like gold nanoparticles (FGN)-based immunochromatographic test strip (ICS) was developed and used for the first time for the rapid simultaneous detection of fumonisin B1 (FB1) and deoxynivalenol (DON) in Chinese traditional medicine. Several experimental conditions affecting the sensitivity of ICS have been investigated, including the type of FGN, the preparation conditions of FGN-monoclonal antibody (MAb) conjugates, and the process parameters of ICS. Under the optimal experimental conditions, the visual limit of detection was 5.0 ng/mL (corresponding to 50 µg/kg in Chinese traditional medicine samples) for both FB1 and DON, and detection can be completed within 5 min. In addition, the natural samples were analyzed using high-performance liquid chromatography (HPLC) or enzyme-linked immunosorbent assay (ELISA), and the results of these methods showed good correlation with those obtained using ICS. The procedure using FGN-based simultaneous ICS was sensitive, rapid, and convenient for on-site detection of a large number of samples.

Systematic review: the etiology of esophageal squamous cell carcinoma in low-income settings.

INTRODUCTION: Esophageal carcinoma causes over 380 000 deaths per year, ranking sixth worldwide in mortality amongst all malignancies. Globally, the squamous cell subtype is most common and accounts for 80% of esophageal cancers. Nonetheless, esophageal squamous cell carcinoma is much more poorly understood than esophageal adenocarcinoma, including what is driving such high prevalences, why it often presents in young patients, and shows such marked geographical delineations Areas covered: The current literature was searched for articles focusing on aetiopathogenesis of squamous cell esophageal carcinoma via a systematic review, particularly in low-resource settings. This was supplemented by papers of interest known to the authors. Expert commentary: Current putative mechanisms include polycyclic aromatic hydrocarbons, nitrosamines, acetaldehyde, cyclo-oxygenase-2 pathways, androgen and their receptor levels, as well as smoking & alcohol, micronutrient deficiencies and diet, mycotoxins, thermal damage, oral hygiene and microbiotal factors, inhaled smoke, viral infections such as HPV, and chronic irritative states. Etiology is likely multifactorial and varies geographically. Though smoking and alcohol play a predominant role in high-income settings, there is strong evidence that mycotoxins, diet and temperature effects may play an under-recognized role in low and middle-income settings.

Genetic modifiers of radon-induced lung cancer risk: a genome-wide interaction study in former uranium miners.

PURPOSE: Radon is a risk factor for lung cancer and uranium miners are more exposed than the general population. A genome-wide interaction analysis was carried out to identify genomic loci, genes or gene sets that modify the susceptibility to lung cancer given occupational exposure to the radioactive gas radon. METHODS: Samples from 28 studies provided by the International Lung Cancer Consortium were pooled with samples of former uranium miners collected by the German Federal Office of Radiation Protection. In total, 15,077 cases and 13,522 controls, all of European ancestries, comprising 463 uranium miners were compared. The DNA of all participants was genotyped with the OncoArray. We fitted single-marker and in multi-marker models and performed an exploratory gene-set analysis to detect cumulative enrichment of significance in sets of genes. RESULTS: We discovered a genome-wide significant interaction of the marker rs12440014 within the gene CHRNB4 (OR = 0.26, 95% CI 0.11-0.60, p = 0.0386 corrected for multiple testing). At least suggestive significant interaction of linkage disequilibrium blocks was observed at the chromosomal regions 18q21.23 (p = 1.2 × 10-6), 5q23.2 (p = 2.5 × 10-6), 1q21.3 (p = 3.2 × 10-6), 10p13 (p = 1.3 × 10-5) and 12p12.1 (p = 7.1 × 10-5). Genes belonging to the Gene Ontology term "DNA dealkylation involved in DNA repair" (GO:0006307; p = 0.0139) or the gene family HGNC:476 "microRNAs" (p = 0.0159) were enriched with LD-blockwise significance. CONCLUSION: The well-established association of the genomic region 15q25 to lung cancer might be influenced by exposure to radon among uranium miners. Furthermore, lung cancer susceptibility is related to the functional capability of DNA damage signaling via ubiquitination processes and repair of radiation-induced double-strand breaks by the single-strand annealing mechanism.

Biomonitoring of Benzene and Effect of Wearing Respirators during an Oil Spill Field Trial at Sea.

Objectives: The main aim of this study was to assess the biological uptake of benzene and polycyclic aromatic hydrocarbons (PAHs) for subjects exposed to fresh crude oil released at sea. Methods: The study included 22 subjects participating in an 'oil-on-water' field trial in the North Sea. Over 2 consecutive days, there were six releases with two different types of fresh crude oils. Exposed subjects (n = 17) were either located in small, open-air boats downwind and close to the released oil (<50 m) or on the main deck of two large vessels further from the released oil (100-200 m). Subjects assumed to be unexposed (n = 5) were located indoors on the command bridge of either vessel. Full-shift personal benzene exposure was monitored with passive thermal desorption tubes (ATD-tubes) packed with Tenax TA and subsequent gas chromatographic analysis. Urine samples were collected before and after work-shift on both days and analyzed for urinary markers of benzene [(S-phenylmercapturic acid (SPMA)] and PAHs [1-hydroxypyrene (1-OH)]. Information about the use of personal protective equipment, smoking habits, location, work tasks, and length of work-shift were recorded by a questionnaire. Results: Subjects located in the small boats downwind and close to the released oil were exposed to relatively high concentrations of benzene (arithmetic mean = 0.2 ppm, range 0.002-1.5 ppm) compared to the occupational exposure limits (OELs) for 8 h (1 ppm) and 12 h (0.6 ppm). Although respirators were available to all exposed subjects, SPMA was detected in post-shift urine (0.5-3.3 µmol mol-1) of five exposed subjects reporting not wearing respirators, all located in the small boats downwind and close to the released oil. For exposed subjects wearing respirators (n = 12), the post-shift urinary SPMA was below the detection limit (0.8 µmol mol-1) even when the benzene exposure exceeded the OELs. Urinary levels of PAH were within the reference range of what is considered as background levels (<0.4 µmol mol-1). Conclusions: During the initial stages of a bulk oil spill at sea, when the evaporation of benzene is at its highest, it is important to use appropriate respirators to prevent biological uptake of benzene.

The citrus flavonone hesperetin attenuates the nuclear translocation of aryl hydrocarbon receptor.

The environmental polycyclic aromatic hydrocarbons (PAH) and dioxins are carcinogens and their adverse effects have been largely attributed to the activation of AhR. Hesperetin is a flavonone found abundantly in citrus fruits and has been shown to be a biologically active agent. In the present study, the effect of hesperetin on the nuclear translocation of AhR and the downstream gene expression was investigated in MCF-7 cells. Confocal microscopy indicated that 7, 12-dimethylbenz[α]anthracene (DMBA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) -induced nuclear translocation of AhR was deterred by hesperetin treatment. The reduced nuclear translocation could also be observed in Western analysis. Reporter-gene assay further illustrated that the induced XRE transactivation was weakened by the treatment of hesperetin. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay demonstrated that the gene expressions of CYP1A1, 1A2, and 1B1 followed the same pattern of AhR translocation. These results suggested that hesperetin counteracted AhR transactivation and suppressed the downstream gene expression.

Polycyclic aromatic hydrocarbons in teas using QuEChERS and HPLC-FLD.

Polycyclic aromatic hydrocarbons (PAHs) are food-processing contaminants considered to be carcinogenic and genotoxic. Due to its drying process stage, teas may be contaminated with PAHs. The aim of the study was to validate an analytical method involving QuEChERS and HPLC-FLD for the determination of PAH4 in teas and evaluate the contamination levels in 10 different types of teas from Brazil. Recoveries varied from 54% to 99% and relative standard deviations from 1% to 21%. Limits of detection and quantification were from 0.03 to 0.3 µg/kg and 0.1 to 0.5 µg/kg, respectively. Mate tea presented the highest PAH levels, with PAH4 varying from 194 to 1795 µg/kg; followed by black (1.8-186 µg/kg), white (24-119 µg/kg), and green teas (3.1-92 µg/kg). Teas with lowest PAH4 were strawberry, lemongrass, peppermint, and boldo. Only trace levels of PAHs were detected in tea infusions, so apparently it would not affect PAH intake by Brazilian population.

Grape skin extract mitigates tissue degeneration, genotoxicity, and oxidative status in multiple organs of rats exposed to cadmium.

The aim of this study was to investigate whether grape skin extract can mitigate the noxious activities induced by cadmium exposure in multiple organs of rats. For this purpose, histopathological analysis for the liver, genotoxicity, and oxidative status in the blood and liver were investigated in this setting. A total of 20 Wistar rats weighing 250 g, on average, and 8 weeks of age were distributed into four groups (n=5) as follows: control group (nontreated group); cadmium group (Cd); and grape skin extract groups (Cd+GS) at 175 or 350 mg/l. Histopathological analysis in liver showed that animals treated with grape skin extract showed improved tissue degeneration induced by cadmium intoxication. Genetic damage was reduced in blood and hepatocytes as indicated by comet and micronucleus assays in animals treated with grape skin extract. Copper-zinc superoxide dismutase and cytochrome c gene expression increased in groups treated with grape skin extract in liver cells. Grape skin extract also reduced the 8-hydroxy-2'-deoxyguanosine levels in liver cells compared with the cadmium group. Taken together, our results indicate that grape skin extract can mitigate tissue degeneration, genotoxicity, and oxidative stress induced by cadmium exposure in multiple organs of Wistar rats.

The protective role of melatonin in porcine oocyte meiotic failure caused by the exposure to benzo(a)pyrene.

STUDY QUESTION: Does melatonin restore the benzo(a)pyrene (BaP)-induced meiotic failure in porcine oocytes? SUMMARY ANSWER: Melatonin effectively inhibits the increased reactive oxygen species (ROS) level and apoptotic rate in BaP-exposed porcine oocytes to recover the meiotic failure. WHAT IS KNOWN ALREADY: BaP, a widespread environmental carcinogen found in particulate matter, 2.5 µm or less (PM2.5), has been shown to have toxicity at the level of the reproductive systems. BaP exposure disrupts the steroid balance, alters the expression of ovarian estrogen receptor and causes premature ovarian failure through the rapid depletion of the primordial follicle pool. In addition, acute exposure to BaP has transient adverse effects on the follicle growth, ovulation and formation of corpora lutea, which results in transient infertility. STUDY DESIGN, SIZE, DURATION: Porcine oocytes were randomly assigned to control, BaP-exposed and melatonin-supplemented groups. BaP was dissolved in dimethylsulphoxide and diluted to a final concentration of 50, 100 or 250 µM with maturation medium, respectively. Melatonin was dissolved in the absolute ethanol and diluted with maturation medium to a final concentration of 1 nM, 100 nM, 10 µM and 1 mM, respectively. The in vitro cultured oocytes from each group after treatment were applied to the subsequent analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Acquisition of oocyte meiotic competence was assessed using immunostaining, fluorescent intensity quantification and/or immunoblotting to analyse the cytoskeleton assembly, mitochondrial integrity, cortical granule dynamics, ovastacin distribution, ROS level and apoptotic rate. Fertilization ability of oocytes was examined by sperm binding assay and IVF. MAIN RESULTS AND THE ROLE OF CHANCE: BaP exposure resulted in the oocyte meiotic failure (P = 0.001) via impairing the meiotic apparatus, showing a prominently defective spindle assembly (P = 0.003), actin dynamics (P < 0.001) and mitochondrion integrity (P < 0.001). In addition, BaP exposure caused the abnormal distribution of cortical granules (P < 0.001) and ovastacin (P = 0.003), which were consistent with the observation that fewer sperm bound to the zona pellucida surrounding the unfertilized BaP-exposed eggs (P < 0.001), contributing to the fertilization failure (P < 0.001). Conversely, melatonin supplementation recovered, at least partially, all the meiotic defects caused by BaP exposure through inhibiting the rise in ROS level (P = 0.015) and apoptotic rate (P = 0.001). LIMITATIONS, REASONS FOR CAUTION: We investigated the negative impact of BaP on the oocyte meiotic maturation in vitro, but not in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our findings not only deeply clarify the potential mechanisms of BaP-induced oocyte meiotic failure, but also extend the understanding about how environmental pollutants influence the reproductive systems in humans. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Natural Science Foundation of China (31571545) and the Natural Science Foundation of Jiangsu Province (BK20150677). The authors have no conflict of interest to disclose.

Assessing cancer hazards of bitumen emissions - a case study for complex petroleum substances.

When assessing cancer hazard and risk associated with a complex petroleum substance, like bitumen emissions, there are often conflicting results related to human, animal and mechanistic studies. Validation of the complex composition to assure that it matches real-world exposures and control of confounders are pivotal factors in study design to allow the necessary read-across during assessments. Several key studies on bitumen emissions in two-year dermal cancer assays reported variable outcomes ranging from high cancer incidence to no cancer incidence. Here, we synthesize findings from published studies to explain the differences and discuss critical factors in cancer hazard evaluation for complex petroleum substances. Using these critical factors, we reviewed relevant human genetic toxicity, mammalian toxicity and mechanistic studies with bitumen to understand the divergence in results. We assess the most reliable and scientifically supported information on the potential carcinogenic hazards of bitumen emissions and comment on quality and completeness of data. Human hazard data are typically considered highest priority because they eliminate the need for interspecies extrapolation and reduce the range of high -to low-dose extrapolation during the risk assessment process. Finally, two well-conducted comprehensive animal studies are discussed that have well-defined test material, exposure concentration and composition representative of worker exposure, evidence of systemic uptake, no confounding exposures and provide consistency across all elements within both studies. Studies that allow effective read-across from human, animal and mechanistic components, control for confounders and are well-validated analytically against workplace exposures, provide the strongest evidence base for evaluating cancer hazard.

Copper (II) binding of NAD(P)H- flavin oxidoreductase (NfoR) enhances its Cr (VI)-reducing ability.

Microbes can reduce hexavalent chromium Cr (VI) to the less toxic and soluble trivalent Cr (III). Copper stimulates microbial reduction of Cr (VI) by the Bacillus, Ochrobactrum, and Gluconobacter species; however, the mechanism remains unclear. In our study, the rate of Cr (VI) reduction by Staphylococcus aureus LZ-01 was increased by 210 % when supplemented with 60 µM Cu (II). A putative NAD(P)H-flavin oxidoreductase gene (nfoR) was upregulated under Cr (VI) stress. NfoR-knockout mutant displayed impaired reduction of Cr (VI) and Cu (II)-enhanced Cr (VI) reduction by nfoR isogenic mutant was attenuated in the presence of Cu (II). In vitro tests showed an increased V max value of 25.22 µM min-1 mg-1 NfoR in the presence of Cu (II). Together, these results indicate that NfoR is responsible for Cu (II) enhancement. Isothermal titration calorimetry (ITC) assays confirmed the interaction of NfoR with Cu (II) at the dissociation constant of 85.5 µM. Site-directed mutagenesis indicates that His100, His128, and Met165 residues may be important for Cu (II) binding, while Cys163 is necessary for the FMN binding of NfoR. These findings show that Cu (II)-enhanced NfoR belongs to a new branch of Cr (VI) reductases and profoundly influences Cr (VI) reduction.

Genotoxicity evaluation of zinc oxide nanoparticles in Swiss mice after oral administration using chromosomal aberration, micronuclei, semen analysis, and RAPD profile.

The expanded uses of zinc oxide nanoparticles (ZnO NPs) have grown rapidly in the field of nanotechnology. Thus, rising production of nanoparticles (NPs) increases the possible risks to the environment and occupationally exposed humans. Hence, it is indispensable to appraise the safety toxicity including genotoxicity for these NPs. In the present study, we have evaluated the genotoxic effect of ZnO NPs after oral administration to Swiss mice at dose levels of 300 and 2000 mg/kg body weight. These doses were administered for 2 days at 24 h apart. Chromosomal aberration (CA) and micronucleus tests were conducted following Organization for Economic Co-operation and Development guidelines. DNA damage was evaluated at 0, 24, 48, and 72 h posttreatment using a randomly amplified polymorphic DNA (RAPD) assay; additionally, semen analyses were also performed at 34.5 days post oral exposure. The reactive oxygen species (ROS), 8-oxo-2'-deoxyguanosine and CAs were increased ( p < 0.05) at the highest dosage (2000 mg/kg) of ZnO NPs compared to controls. Aberrant sperm morphology with reduced sperm count and motility were also present ( p < 0.05) in the high-dose group. Based on the RAPD assay, the genomic template stability within the high-dose group (<90%) was less than the controls (100%). The results suggested that ZnO NPs are mildly genotoxic in a dose-related manner and this toxicity were induced by generation of ROS.

Oil Spill Field Trial at Sea: Measurements of Benzene Exposure.

OBJECTIVES: Characterize personal exposure to airborne hydrocarbons, particularly carcinogenic benzene, during spill of two different fresh crude oils at sea. METHODS: The study included 22 participants taking part in an «oil on water¼ field trial in the North Sea. Two types of fresh crude oils (light and heavy) were released six times over two consecutive days followed by different oil spill response methods. The participants were distributed on five boats; three open sampling boats (A, B, and C), one release ship (RS), and one oil recovery (OR) vessel. Assumed personal exposure was assessed a priori, assuming high exposure downwind and close to the oil slick (sampling boats), low exposure further downwind (100-200 m) and upwind from the oil slick (main deck of RS and OR vessel), and background exposure indoors (bridge of RS/OR vessel). Continuous measurements of total volatile organic compounds in isobutylene equivalents were performed with photoionization detectors placed in all five boats. Full-shift personal exposure to benzene, toluene, ethylbenzene, xylenes, naphthalene, and n-hexane was measured with passive thermal desorption tubes. RESULTS: Personal measurements of benzene, averaged over the respective sample duration, on Day 1 showed that participants in the sampling boats (A, B, and C) located downwind and close to the oil slick were highest exposed (0.14-0.59 ppm), followed by participants on the RS main deck (0.02-0.10 ppm) and on the bridge (0.004-0.03 ppm). On Day 2, participants in sampling boat A had high benzene exposure (0.87-1.52 ppm) compared to participants in sampling boat B (0.01-0.02 ppm), on the ships (0.06-0.10 ppm), and on the bridge (0.004-0.01 ppm). Overall, the participants in the sampling boats had the highest exposure to all of the compounds measured. The light crude oil yielded a five times higher concentration of total volatile organic compounds in air in the sampling boats (max 510 ppm) than the heavy crude oil (max 100 ppm) but rapidly declined to <20 ppm within 24 min after release of oil, indicating short periods of exposure. CONCLUSIONS: The personal exposure to benzene downwind and close to the oil slick during spills of light crude oil was relatively high, with concentration levels approaching the occupational exposure limits for several participants. For bulk spill scenarios like in this study, cleanup should not be initiated the first 30-60 min to allow for evaporation, while appropriate personal protective equipment should be used in continuous spills when working downwind and close to the oil slick.

Protective Effect of Selenium on Aflatoxin B1-Induced Testicular Toxicity in Mice.

Aflatoxins have been considered as one of the major risk factors of male infertility, and aflatoxin B1 (AFB1) is the most highly toxic and prevalent member of the aflatoxins family. Selenium (Se), an essential nutritional trace mineral for normal testicular development and male fertility, has received extensive intensive on protective effects of male reproductive system due to its potential antioxidant and activating testosterone synthesis. To investigate the protective effect of Se on AFB1-induced testicular toxicity, the mice were orally administered with AFB1 (0.75 mg/kg) and Se (0.2 mg/kg or 0.4 mg/kg) for 45 days. We found that that Se elevated testes index, sperm functional parameters (concentration, malformation, and motility), and the level of serum testosterone in AFB1-exposed mice. Moreover, our results showed that Se attenuated the AFB1-induced oxidative stress and the reduction of testicular testosterone synthesis enzyme protein expression such as steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), and 17ß-hydroxysteroid dehydrogenase (17ß-HSD) in AFB1-exposed mice. These results demonstrated that Se conferred protection against AFB1-induced testicular toxicity and can be attributed to its antioxidant and increased testosterone level by stimulating protein expression of StAR and testosterone synthetic enzymes.