Journal of Environmental Science and Health Part C-Toxicology and Carcinogenesis最新文献

Synaptic plasticity plays an important role in learning and memory in the developing hippocampus. However, the precise molecular mechanism in lead exposure models remains to be studied. UCP2, an inner mitochondrial anion carrier, regulates synaptic plasticity through uncoupling neurons. And hnRNP K, an RNA binding protein, plays a role in modulating the expression of transcripts coding synaptic plasticity. We aim to investigate whether lead exposure affects UCP2 and hnRNP K expression levels. The Sprague-Dawley rats were exposed to different lead acetate concentrations (0 g/l, 0.5 g/l, 2.0 g/l) during gestational and lactational periods. PC12 cells were also exposed to different lead acetate concentrations (0 μM, 1 μM and 100 μM). We found that the expression levels of UCP2 and hnRNP K had significant declines in the lead exposure rat hippocampus and PC12 cells. Furthermore, the up-regulation of hnRNP K expression level could reverse the expression level of UCP2 in lead exposure models. In conclusion, these results suggest that lead exposure can reduce the expression level of UCP2 which is mediated by decreasing the expression level of hnRNP K.

Fumonisins, discovered in 1988 are a group of naturally occurring toxins produced by fusarium pathogenic fungi. Besides their presence in animal feeds, contamination of human foods such as corn, millet, oats, rye, barley, wheat and their products are widespread. Exposure to fumonisins results in species and organ specific toxicities including neurological disorders among equids, pulmonary edema in swine, esophageal cancer in humans and both kidney and liver related toxicities in rodents. This review seeks to consolidate groundbreaking research on the science of fumonisins toxicity, highlight recent progress on fumonisins research, and provide an overview of plausible mechanistic biomarkers for fumonisins exposure assessment.

The use of fluoride (F) for therapeutic purposes is controversial and its toxicity is a health problem. The aim of this study was to evaluate the effect of F on endochondral ossification in growing rats. Twenty-four rats of 21 days were divided into 4 groups which received 0, 20, 40 or 80 μmol F/100 g body weight/day for 30 days, through an orogastric tube. Histological evaluation of growth plate cartilage (GPC) and primary and secondary bone were analyzed on sections of the metaphysis of tibias. Total thickness of the GPC (GPC.Th), thickness of resting zone (RZ.Th), proliferative zone (PZ.Th) and hypertrophic zone (HZ.Th); bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and apoptosis by the TUNEL were measured. A hyperplasia of the proliferative zone and a significant increase in PZ.Th with 40 and 80 μmol F without changes in GPC.Th were found. In the secondary trabecular bone, presence of immature trabeculae, peritrabecular inflammatory foci and sinusoidal dilatation were observed. A significant decrease in BV/TV was also found due to a decrease in Tb.Th and a progressive increase was observed in the number of apoptotic nuclei as the dose of F increased. In conclusion, results suggest that prolonged administration (30 days) of F negatively affect the endochondral ossification with increased chondrocyte proliferation and delayed maturity of new bone, causing inflammatory damage, edema, and increased apoptotic bone cells.

We recently established a genotoxic mechanism mediated by a set of (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts, which lead to pyrrolizidine alkaloid (PA)-induced liver tumor initiation. This mechanism is involved in the metabolism of a series of carcinogenic PAs and PA N-oxides in rats in vivo and in vitro. There is a correlation between the order of liver tumor potency and the level of DHP-DNA adduct formation. Thus, these DHP-DNA adducts can be potential biomarkers of PA and PA N-oxide exposure and liver tumor initiation. To establish the generality of this mechanism, in the present study, we examined the metabolism of 13 potential carcinogenic PAs, 1 non-carcinogenic PA, and 5 PA N-oxides by male rat primary hepatocytes. With the exception of the nontoxic PA and vehicle control, all treated groups produced identical set of DHP-DNA adducts. These results support a general genotoxic mechanism mediated by the formation of characteristic DHP-DNA adducts leading to PA-induced liver tumor initiation.

Glyphosate is a toxic environmental pollutant that has the ability to induce biochemical and physiological alterations in living organisms. Several studies have focused on the research of protective techniques against the stress induced by this contaminant. In this context, we studied the protective effect of Spirulina against the disturbances induced by glyphosate. A biomarker approach was adopted to determine the impact of glyphosate, Spirulina and their mixture, during two time slots (4 and 7 days), on Mytilus galloprovincialis. Glyphosate treated mussels revealed significantly increased malondialdehyde and decreased acetylcholinesterase (AChE) levels. Spirulina normalized catalase (CAT), glutathione-S-transferase (GST), and AChE activities. Furthermore, it reduced glyphosate-induced malondialdehyde (MDA) levels. The current study suggests a protective effect of Spirulina against glyphosate-induced oxidative stress by strengthening the antioxidant system, sequestering ROS and inhibiting cellular damage.

Nano-metals, nano-metal oxides, and carbon-based nanomaterials exhibit superior solar-to-chemical/photo-electron transfer properties and are potential candidates for environmental remediations and energy transfer. Recent research effort focuses on enhancing the efficiency of photoinduced electron-hole separation to improve energy transfer in catalytic reactions. Electron spin resonance (ESR) spectroscopy has been used to monitor the generation of electron/hole and reactive oxygen species (ROS) during nanomaterial-mediated photocatalysis. Using ESR coupled with spin trapping and spin labeling techniques, the underlying photocatalytic mechanism involved in the nanomaterial-mediated photocatalysis was investigated. In this review, we briefly introduced ESR principle and summarized recent advancements using ESR spectroscopy to characterize electron-hole separation and ROS production by different types of nanomaterials.

As a widespread pollutant, glyphosate (GLY) adversely affects the aquatic environment and can impair the reproductive ability and functions of fish. The purpose of the current study was to assess in vitro effect of GLY on rainbow trout (Oncorhynchus mykiss) sperm cells. The sperm cells were exposed to different GLY concentrations (2.5, 5, 10 mg/L). Sperm motility parameters were analyzed with computer assisted sperm analysis. DNA fragmentation (%) was measured by the comet assay using fluorescence microscopy. With increased GLY concentration, sperm motility and duration decreased after exposure. DNA fragmentation (% DNA in tail) in sperm cells was higher in treatments containing GLY than control (p < 0.05). Consequently, sperm cells are sensitive to low doses of GLY, and this can negatively affect natural populations.

Molecular alterations as a result of exposure to low doses of high linear energy transfer (LET) radiation can have deleterious short- and long-term consequences on crew members embarking on long distance space missions. Oxygen ions (¹⁶O) are among the high LET charged particles that make up the radiation environment inside a vehicle in deep space. We used mass spectrometry-based metabolomics to characterize urinary metabolic profiles of male C57BL/6J mice exposed to a single dose of 0.1, 0.25 and 1.0 Gy of ¹⁶O (600 MeV/n) at 10 and 30 days post-exposure to delineate radiation-induced metabolic alterations. We recognized a significant down regulation of several classes of metabolites including cresols and tryptophan metabolites, ketoacids and their derivatives upon exposure to 0.1 and 0.25 Gy after 10 days. While some of these changes reverted to near normal by 30 days, some metabolites including p-Cresol sulfate, oxalosuccinic acid, and indoxylsulfate remained dysregulated at 30 days, suggesting long term prognosis on metabolism. Pathway analysis revealed a long-term dysregulation in multiple pathways including tryptophan and porphyrin metabolism. These results suggest that low doses of high-LET charged particle irradiation may have long-term implications on metabolic imbalance.

Astronauts embarking on deep space missions are at high risk of long-term exposure to low doses of high linear energy transfer (LET) radiation, which can contribute to the development of cancer and multiple degenerative diseases. However, long term effects of exposure to low doses of high LET radiation in plasma metabolite profiles have not been elucidated. We utilized an untargeted metabolomics and lipidomics approach to analyze plasma obtained from adult male Long Evans rats to determine the longitudinal effects of low-dose proton and low-dose oxygen ion whole-body irradiation on metabolic pathways. Our findings reveal that radiation exposure induced modest changes in the metabolic profiles in plasma, 7 months after exposure. Furthermore, we identified some common metabolite dysregulations between protons and oxygen ions, which may indicate a similar mechanism of action for both radiation types.

Cancer is a main concern for human health and there is a need of alternative methodologies to rapidly screen large quantitative of compounds that may represent a toxicological risk. Here a statistical analyses is performed on a benchmark database of experimental Ames data to identify chemical descriptors discriminating mutagens and non-mutagens. A total of 53 activating and deactivating modulators are identified, that flagged respectively a percentage of mutagen and non-mutagen up to 87%. Modulators are further combined to form synergistic cross-terms, accounting for the effect that combined properties may have on the final toxicity. Exclusion rules are defined as exception to the modulators. Synergistic cross-terms and exclusion rules improve the enrichment of mutagens/non-mutagens with respect of the original abundance in the dataset to values higher than 95%. The external predictivity of modulators and cross-terms reach balanced accuracy up to 0.775 that is analogous to other mutagenicity models from the literature, confirming the suitability of the rules to real-life screening of chemicals. Modulators are discussed for their mechanistic link to mutagenicity. This analysis confirms the key role of some properties (polarizability, shape, mass, presence of reactive functional groups or unsaturated planar systems) as driving elements for the initiation of the mutagenicity.