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Our results show that both nPS are easily internalized by Caco-2 cells in a concentration-dependent manner, but no relevant toxic effects are observed under the analyzed exposure conditions.

Cerium oxide nanoparticles (CeO2-NP) present two different oxidation states what can suppose an auto-regenerative redox cycle. Potential applications of CeO2-NP to quench reactive oxygen species (ROS) in biological systems are currently being investigated. In this context, CeO2-NP may represent a novel agent to protect cells and tissues against oxidative damage by its regenerative free radical-scavenging properties. In this study, we have used a human epithelial lung cell line, BEAS-2B, as a model to study the possible antioxidant and anti-genotoxic effect of CeO2-NP in a pulmonary-like system. We have assessed the protective effect of CeO2-NP pre-treatment in front of a well-defined oxidative stress-inducing agent (KBrO3). Different endpoints like toxicity, intracellular ROS induction, genotoxicity and DNA oxidative damage (comet assay), and gene expression alterations have been evaluated. The obtained results confirmed the antioxidant properties of CeO2-NP. Thus, its pre-treatment significantly reduced the intracellular production of ROS induced by KBrO3. Similarly, a reduction in the levels of DNA oxidative damage, as measured with the comet assay complemented with formamidopyrimidine DNA glycosylase enzyme, was also observed. Pre-treatment of BEAS-2B cells with CeO2-NP (at 2.5 µg/mL) slightly increased the viability of cells treated with KBrO3 as well as down-regulated the expression of the Ho1 and Sod2 genes involved in the oxidative Nrf2 pathway. Our finding would support the potential usefulness of CeO2-NP as a pharmacological agent to be used against diseases caused by oxidative stress.

People are exposed to arsenic compounds environmentally, occupationally or therapeutically. In some areas, where arsenic is present in high proportions in the drinking water, this exposure represents an important health concern. Chronic exposure to arsenic leads to hyperkeratosis and loss of skin pigmentation, as well as to significant increases of different types of cancer in skin, lung, bladder and liver; in addition, other pathologies, such as vascular diseases, hepatotoxicity and diabetes, have also been related to arsenic exposure. Since high interindividual variability is observed among people exposed to equivalent doses, genetic susceptibility factors have been postulated to be involved. When inorganic arsenic enters into the body it undergoes metabolic conversion, in a process where methylation plays a crucial role. Trivalent forms, both inorganic and organic, are the most toxic and genotoxic and, for this reason, metabolic variations owing to variant alleles in genes involved in such a process have been the aim of several studies. Genes involved in other mechanisms, such as antioxidant defense and DNA-repair lesions, among others, have also been the subject of association studies. A survey of those studies related to individual susceptibility is summarized here. Results with genes involved in folate one-carbon metabolism and in arsenic transport across the cell membrane provide promising data for future studies.

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Neurofibromatosis type 1 (NF1) is a hereditary disorder caused by mutations in the NF1 gene. Detecting mutation in NF1 is hindered by the gene's large size, the lack of mutation hotspots, the presence of pseudogenes, and the wide variety of possible lesions. We developed a method for detecting germline mutations by combining an original RNA-based cDNA-PCR mutation detection method and denaturing high-performance liquid chromatography (DHPLC) with multiplex ligation-dependent probe amplification (MLPA). The protocol was validated in a cohort of 56 blood samples from NF1 patients who fulfilled NIH diagnostic criteria, identifying the germline mutation in 53 cases (95% sensitivity). The efficiency and reliability of this approach facilitated detection of different types of mutations, including single-base substitutions, deletions or insertions of one to several nucleotides, microdeletions, and changes in intragenic copy number. Because mutational screening for minor lesions was performed using cDNA and the characterization of mutated alleles was performed at both the RNA and genomic DNA level, the analysis provided insight into the nature of the different mutations and their effect on NF1 mRNA splicing. After validation, we implemented the protocol as a routine test. Here we present the overall unbiased spectrum of NF1 mutations identified in 93 patients in a cohort of 105. The results indicate that this protocol is a powerful new tool for the molecular diagnosis of NF1.