Effects of Loud Noise Exposure on DNA Integrity in Rat Adrenal Gland

Loud noise is generally considered an environmental stressor causing negative effects on acoustic, cardiovascular, nervous, and endocrine systems. In this study, we investigated the effects of noise exposure on DNA integrity in rat adrenal gland evaluated by the comet assay. The exposure to loud noise (100 dBA) for 12 hr caused a significant increase of DNA damage in the adrenal gland. Genetic alterations did not decrease 24 hr after the cessation of the stimulus. We hypothesize that an imbalance of redox cell status is responsible for the induction and persistence of noise-induced cellular damage

Effects of Loud Noise Exposure on DNA Integrity in Rat Adrenal Gland

Loud noise is generally considered an environmental stressor causing negative effects on acoustic, cardiovascular, nervous, and endocrine systems. In this study, we investigated the effects of noise exposure on DNA integrity in rat adrenal gland evaluated by the comet assay. The exposure to loud noise (100 dBA) for 12 hr caused a significant increase of DNA damage in the adrenal gland. Genetic alterations did not decrease 24 hr after the cessation of the stimulus. We hypothesize that an imbalance of redox cell status is responsible for the induction and persistence of noise-induced cellular damage

Drugs targeting the mitochondrial pore act as citotoxic and cytostatic agents in temozolomide-resistant glioma cells

<p>Abstract</p> <p>Background</p> <p>High grade gliomas are one of the most difficult cancers to treat and despite surgery, radiotherapy and temozolomide-based chemotherapy, the prognosis of glioma patients is poor. Resistance to temozolomide is the major barrier to effective therapy. Alternative therapeutic approaches have been shown to be ineffective for the treatment of genetically unselected glioma patients. Thus, novel therapies are needed. Mitochondria-directed chemotherapy is an emerging tool to combat cancer, and inner mitochondrial permeability transition (MPT) represents a target for the development of cytotoxic drugs. A number of agents are able to induce MPT and some of them target MPT-pore (MPTP) components that are selectively up-regulated in cancer, making these agents putative cancer cell-specific drugs.</p> <p>Objective</p> <p>The aim of this paper is to report a comprehensive analysis of the effects produced by selected MPT-inducing drugs (Betulinic Acid, Lonidamine, CD437) in a temozolomide-resistant glioblastoma cell line (ADF cells).</p> <p>Methods</p> <p>EGFRvIII expression has been assayed by RT-PCR. EGFR amplification and PTEN deletion have been assayed by differential-PCR. Drugs effect on cell viability has been tested by crystal violet assay. MPT has been tested by JC1 staining. Drug cytostatic effect has been tested by mitotic index analysis. Drug cytotoxic effect has been tested by calcein AM staining. Apoptosis has been assayed by Hoechst incorporation and Annexine V binding assay. Authophagy has been tested by acridine orange staining.</p> <p>Results</p> <p>We performed a molecular and genetic characterization of ADF cells and demonstrated that this line does not express the EGFRvIII and does not show EGFR amplification. ADF cells do not show PTEN mutation but differential PCR data indicate a hemizygous deletion of PTEN gene. We analyzed the response of ADF cells to Betulinic Acid, Lonidamine, and CD437. Our data demonstrate that MPT-inducing agents produce concentration-dependent cytostatic and cytotoxic effects in parallel with MPT induction triggered through MPTP. CD437, Lonidamine and Betulinic acid trigger apoptosis as principal death modality.</p> <p>Conclusion</p> <p>The obtained data suggest that these pharmacological agents could be selected as adjuvant drugs for the treatment of high grade astrocytomas that resist conventional therapies or that do not show any peculiar genetic alteration that can be targeted by specific drugs.</p

Eco-Friendly Engineered Nanomaterials Coupled with Filtering Fine-Mesh Net as a Promising Tool to Remediate Contaminated Freshwater Sludges: An Ecotoxicity Investigation

The use of eco-friendly engineered nanomaterials represents a recent solution for an effective and safe treatment of contaminated dredging sludge. In this study, an eco-designed engineered material based on cross-linked nanocellulose (CNS) was applied for the first time to decontaminate a real matrix from heavy metals (namely Zn, Ni, Cu, and Fe) and other undesired elements (mainly Ba and As) in a lab-scale study, with the aim to design a safe solution for the remediation of contaminated matrices. Contaminated freshwater sludge was treated with CNS coupled with a filtering fine-mesh net, and the obtained waters were tested for acute and sublethal toxicity. In order to check the safety of the proposed treatment system, toxicity tests were conducted by exposing the bacterium Aliivibrio fischeri and the crustacean Heterocypris incongruens, while subtoxicity biomarkers such as lysosomal membrane stability, genetic, and chromosomal damage assessment were performed on the freshwater bivalve Dreissena polymorpha. Dredging sludge was found to be genotoxic, and such genotoxicity was mitigated by the combined use of CNS and a filtering fine-mesh net. Chemical analyses confirmed the results by highlighting the abetment of target contaminants, indicating the present model as a promising tool in freshwater sludge nanoremediation

Cellular Responses Induced by Zinc in Zebra Mussel Haemocytes. Loss of DNA Integrity as a Cellular Mechanism to Evaluate the Suitability of Nanocellulose-Based Materials in Nanoremediation

: Zinc environmental levels are increasing due to human activities, posing a threat to ecosystems and human health. Therefore, new tools able to remediate Zn contamination in freshwater are highly recommended. Specimens of Dreissena polymorpha (zebra mussel) were exposed for 48 h and 7 days to a wide range of ZnCl2 nominal concentrations (1–10–50–100 mg/L), including those environmentally relevant. Cellulose-based nanosponges (CNS) were also tested to assess their safety and suitability for Zn removal from freshwater. Zebra mussels were exposed to 50 mg/L ZnCl2 alone or incubated with 1.25 g/L of CNS (2 h) and then removed by filtration. The effect of Zn decontamination induced by CNS has been verified by the acute toxicity bioassay Microtox®. DNA primary damage was investigated by the Comet assay; micronuclei frequency and nuclear morphological alterations were assessed by Cytome assay in mussels’ haemocytes. The results confirmed the genotoxic effect of ZnCl2 in zebra mussel haemocytes at 48 h and 7-day exposure time. Zinc concentrations were measured in CNS, suggesting that cellulose-based nanosponges were able to remove Zn(II) by reducing its levels in exposure waters and soft tissues of D. polymorpha in agreement with the observed restoration of genetic damage exerted by zinc exposure alon

Nanoparticled Titanium Dioxide to Remediate Crude Oil Exposure. An In Vivo Approach in Dicentrarchus labrax

The contamination of marine water bodies with petroleum hydrocarbons represents a threat to ecosystems and human health. In addition to the surface slick of crude oil, the water-soluble fraction of petroleum is responsible for the induction of severe toxic effects at different cellular and molecular levels. Some petroleum-derived hydrocarbons are classified as carcinogenic and mutagenic contaminants; therefore, the oil spill into the marine environment can have long term consequences to the biota. Therefore, new tools able to remediate crude oil water accommodation fraction pollution in marine water are highly recommended. Nanomaterials were recently proposed in environmental remediation processes. In the present in vivo study, the efficacy of pure anatase titanium nanoparticles (n-TiO2) was tested on Dicentrarchus labrax exposed to the accommodated fraction of crude oil. It was found that n-TiO2 nano-powders themselves were harmless in terms of DNA primary damage, and the capability of pure anatase n-TiO2 to lower the levels of DNA damage induced by a mixture of genotoxic pollutant was revealed. These preliminary results on a laboratory scale are the prerequisite for deepening this new technology for the abatement of the cellular effects related with oil spill pollutants released in marine environments

The comet assay as a method of assessment of neurotoxicity - Usefulness for drugs of abuse

Comet assay is a quick and versatile method for assessing DNA damage in individual cells. It allows the detection of single and double DNA strand breaks, as well as the presence of alkali labile sites. DNA breaks may represent the direct effect of some damaging agent, or they may be intermediates in cellular repair. DNA strand breaks may also come from the action of free radicals generated by oxidative stress processes. The present article summarizes some data from our and other groups underlining the suitability of the Comet assay in assessing neurotoxicity and its potential in evaluating drugs of abuse-related genotoxicity

Genotoxic potential of TiO(2) on bottlenose dolphin leukocytes

Titanium dioxide is extensively used in a variety of products, including industrial materials and cosmetics. Studies mainly performed on human cell lines and in vivo exposure on experimental animals have raised concern about the toxic effects of ultrafine titanium dioxide; however, scarce information is available about its impact on aquatic life. The aim of this article was to assess the genotoxic potential of TiO(2) (anatase and rutile) on bottlenose dolphin leukocytes. Blood samples were obtained from four male and one female specimens reared at the Adriatic SeaWorld "Oltremare" (Riccione, Italy). Leukocytes were isolated by the lyses procedure and in vitro exposed to TiO(2) in RPMI. Experimental solutions were sonicated immediately before dosing the cells. Three exposure times (4, 24 and 48 h) and three doses (20, 50 and 100 microg/ml) were tested. Genotoxicity was detected by the single-cell gel electrophoresis (or comet assay) at pH > or = 13, assessing single/double-strand breaks and alkali-labile sites. Cytotoxicity was also detected by the Trypan blue exclusion method. Results showed that both the crystalline forms of TiO(2) were genotoxic for bottlenose dolphin leukocytes, with a statistically significant increase of DNA fragmentation after exposure to 50 and 100 microg/ml for 24 and 48 h. Although preliminary, these are the first data regarding the genetic susceptibility of toothed cetaceans toward an "emerging" pollutant, such as TiO(2) particles