The use of biomarkers as tools to evaluate genotoxicity is increasing recently. Methods that have been used previously to evaluate genomic instability are frequently expensive, complicated, and invasive. The micronuclei (MN) and nuclear abnormalities (NA) technique in buccal cells offers a great opportunity to evaluate in a clear and precise way the appearance of genetic damage whether it is present as a consequence of occupational or environmental risk. This technique is reliable, fast, relatively simple, cheap, and minimally invasive and causes no pain. So, it is well accepted by patients; it can also be used to assess the genotoxic effect derived from drug use or as a result of having a chronic disease. Furthermore the beneficial effects derived from changes in life style or taking additional supplements can also be evaluated. In the present paper, we aim to focus on the explanation of MN test and its usefulness as a biomarker; we further give details about procedures to perform and interpret the results of the test and review some factors that could have an influence on the results of the technique.
Posttranslational modifications (PTMs) are defined as covalent modifications occurring in a specific protein amino acid in a time- and signal-dependent manner. Under physiological conditions, proteins are posttranslationally modified to carry out a large number of cellular events from cell signaling to DNA replication. However, an absence, deficiency, or excess in PTMs of a given protein can evolve into a target to trigger autoimmunity, since PTMs arise in the periphery and may not occur in the thymus; hence, proteins with PTMs never tolerize developing thymocytes. Consequently, when PTMs arise during cellular responses, such as inflammation, these modified self-antigens can be taken up and processed by the antigen-presenting cells (APCs). Autoreactive T cells, which recognize peptides presented by APCs, can then infiltrate into host tissue where the modified antigen serves to amplify the autoimmune response, eventually leading to autoimmune pathology. Furthermore, a PTM occurring in an amino acid residue can induce changes in the net charge of the protein, leading to conformational modifications in the tertiary and quaternary structure of the protein, especially interaction with human leukocyte antigen (HLA) molecules. Molecular mimicry (MM) was until now the prevailing hypothesis explaining generation of autoimmunity; nevertheless, experimental animal models need inflammation via infection or other immunogens to ensure autoimmunity; MM alone is not sufficient to develop autoimmunity. PTMs could arise as an additive factor to MM, which is required to start an autoimmune response. PTMs have been found to be present in different pathologic conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome, and primary biliary cirrhosis. The aim of the present review is to expose protein posttranslational modifications and the evidence suggesting their role in the generation of autoimmunity.
During the last 3 decades, there has been a slow advance to obtain new treatments for malignant melanoma that improve patient survival. In this work, we present a systematic study focused on the antiproliferative and antitumour effect of AgNPs. These nanoparticles are fully characterized, are coated with polyvinylpyrrolidone (PVP), and have an average size of 35±15 nm and a metallic silver content of 1.2% wt. Main changes on cell viability, induction of apoptosis and necrosis, and ROS generation were found on B16-F10 cells after six hours of exposure to AgNPs (IC50=4.2 μg/mL) or Cisplatin (IC50=2.0 μg/mL). Despite the similar response for both AgNPs and Cisplatin on antiproliferative potency (cellular viability of 53.95±1.88 and 53.62±1.04) and ROS production (20.27±1.09% and 19.50±0.35%), significantly different cell death pathways were triggered. While AgNPs induce only apoptosis (45.98±1.88%), Cisplatin induces apoptosis and necrosis at the same rate (22.31±1.72% and 24.07±1.10%, respectively). In addition to their antiproliferative activity, in vivo experiments showed that treatments of 3, 6, and 12 mg/kg of AgNPs elicit a survival rate almost 4 times higher (P<0.05) compared with the survival rate obtained with Cisplatin (2 mg/kg). Furthermore, the survivor mice treated with AgNPs do not show genotoxic damage determined by micronuclei frequency quantification on peripheral blood cells. These results exhibit the remarkable antitumour activity of a nongenotoxic AgNP formulation and constitute the first advance toward the application of these AgNPs for melanoma treatment, which could considerably reduce adverse effects provoked by currently applied chemotherapeutics.
Objective:To evaluate genotoxicity of anabolic androgenic steroids (AAS) in male bodybuilders by a micronucleus assay in buccal mucosa cells.Methods:11 male bodybuilders volunteered to participate in this study and two groups were formed: group 1 (n = 6), without AAS consumption and group 2 (n = 5), with AAS consumption. A sample of buccal epithelium was taken from each participant once a week for 6 weeks. Samples were fixed, stained and analysed by a light microscope, and 2000 cells were counted from each slide. Results are expressed as micronucleated cells (MNC) per 1000 cells and were analysed by the Mann–Whitney U test and Wilcoxon’s test.Results:A marked increased in MNC was seen in bodybuilders with AAS consumption compared with those without AAS consumption (mean (SD) 4.1 (2.4) MNC/1000 cells vs 0.4 (0.4) MNC/1000 cells, respectively; p<0.004). Intragroup comparisons showed no differences in the MNC frequencies during the sampling time in group 1, whereas the MNC frequency in group 2 varied significantly, reaching the highest MNC frequencies in the third and fourth week of sampling (5.9 (2.4) MNC/1000 cells; 5.8 (1.8) MNC/1000 cells, respectively); frequency in the first sampled week was 1.1 (0.1) MNC/1000 cells. Significant differences in all sampled weeks were found between the two groups.Conclusion:AAS consumption increased the frequency of MNC from buccal mucosa in bodybuilders.
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