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Hazard Characterization and Dose–Response Assessment
Published in Ted W. Simon, Environmental Risk Assessment, 2019
Genotoxicity is the ability of substances to damage DNA and/or cellular components regulating the fidelity of the genome—such as the spindle apparatus, topoisomerases, DNA repair systems, and DNA polymerases. The oldest, least expensive, and least predictive test is the bacterial reverse mutation assay, or Ames Test. The in vitro micronucleus test uses mammalian cell lines or cultures of primary human cells and looks for micronuclei or chromosomal aberrations. Micronuclei are infrequent third nuclei formed during cell division that contain chromosome fragments. The dose-dependent frequency of micronuclei suggests potential genotoxicity. In vivo genotoxicity tests are most often performed in transgenic animals and look for specific effects depending on the transgenic species.157
Genotoxicity and Air Pollutions
Published in Brian D. Fath, Sven E. Jørgensen, Megan Cole, Managing Air Quality and Energy Systems, 2020
Eliane Tigre Guimarães, Andrea Nunes Vaz Pedroso
Among mutagenic tests, the micronucleus test is widely used because it is applicable with different eukaryotic organisms. By definition, the micronucleus is a small nucleus, regarded as a product of breakage of genomic DNA of eukaryotic cells. During cell division, genetic material is duplicated and distributed equally between two daughter cells. Radiation and chemicals can cause chromosomal breakage or damage, affecting the distribution of genetic material between daughter cells. Parts or fragments of chromosomes resulting from this damage can be distributed to any of the daughter cells. It is not incorporated into the new core; they may be presented in the form of micronuclei clearly observable on optical microscope.[35]
Image-Based High-Content Analysis, Stem Cells and Nanomedicines: A Novel Strategy for Drug Discovery
Published in Dan Peer, Handbook of Harnessing Biomaterials in Nanomedicine, 2021
Leonardo J. Solmesky, Yonatan Adalist, Miguel Weil
Micronuclei are small, stainable bodies outside the nucleus that form when a chromosome or its fragment is not incorporated into one of the daughter nuclei during cell division, constituting a hallmark of genetic toxicity. Therefore, it is widely used as an assay for risk assessment of the cancer-inducing potential of a new drug, which is required by regulatory agencies for drug approval. The image-based high-content analysis of micronuclei has been shown to have good correlation with in vivo micronucleus assays [63].
Genotoxic risk in occupational exposure to petrol and its amelioration by vitamin C and vitamin E
Published in Archives of Environmental & Occupational Health, 2022
Amrin Shaikh, Puranjay Chandel, Divya Chandel
Micronucleus (MN) frequency in cytokinesis-block Peripheral Blood Lymphocyte Culture (PBLC) has become one of the best-established biomarkers for studying DNA damage occurring in vivo in humans7 and any compound which can induce chromosomal aberrations can lead to induction of micronuclei (MN). The observed highly significant increase in MN frequencies in present study can be attributed to exposure of complex chemical mixtures of petrol and lack of protective measures which can also lead to predisposition to cancer. Previous studies indicate that micronuclei frequency increased significantly in cancer patients14,15 and also in smokers leading to cancerous condition.16 Studies on various occupational workers exposed to aromatic hydrocarbons showed notably increased MN frequency.17,18 The MN assay can be used as a crucial biomarker for genotoxicity analysis in individuals occupationally exposed to petrol for long-term risk management.
Steroid androgen 17 alpha methyltestosterone used in fish farming induces biochemical alterations in zebrafish adults
Published in Journal of Environmental Science and Health, Part A, 2020
Carla Letícia Gediel Rivero-Wendt, Ana Luisa Miranda-Vilela, Inês Domingues, Rhaul Oliveira, Marta Sofia Monteiro, Monica A. M. Moura-Mello, Rosemary Matias, Amadeu Mortágua Velho Maia Soares, Cesar Koppe Grisolia
As previously mentioned, steroid hormones are considered non-genotoxic and non-carcinogenic,[4,7,15] although reported results are still controversial. In this respect, our results showed low genotoxic potential of MT, inducing micronucleus, nuclear abnormalities and DNA damage in Danio rerio, depending on the use of MT or cMT, gender and tested concentrations. The use of cMT in fish farms (e.g. Brazilian farms) may give rise to reproductive anomalies in Oreochromis niloticus juveniles, such as a decrease in oocyte maturation in juveniles after exposure for 28 days at a concentration of 0.06 µg/L MT.[7] Khalil et al.[45] carried out a study with tilapia treated with methyltestosterone to induce sex reversion, and four months later detected increased DNA fragmentation through the DNA gel electrophoresis laddering assay as compared to the untreated control. The frequency of micronuclei is related to the genetic instability produced by a toxic agent.[46] Abo-Al-Ela et al.[47] found an increase in the MN frequency in Nile tilapia injected with 25 µg/g MT compared to controls, which demonstrates a genotoxic effect for this androgen. However, in another study, no genetic damage was found after exposure for 96 h at the concentration of 10 µg/L of MT analyzed by the MN test,[4] suggesting that Danio rerio could have greater sensitivity to the analyzed compounds when compared to Oreochromis niloticus and Astyanax bimaculatus.
Could fluoride be considered a genotoxic chemical agent in vivo? A systematic review with meta-analysis
Published in International Journal of Environmental Health Research, 2023
Giovana Wagner Branda Drummond, Wilton Mitsunari Takeshita, Glaucia Monteiro de Castro, Jean Nunes dos Santos, Patricia Ramos Cury, Ana Claudia Muniz Renno, Daniel Araki Ribeiro
Micronucleus (MN) is an assay that identifies a chromosome or a fragment of chromosome that during mitosis was not included in the nucleus of the cell. Its size corresponds to 1/3 to 1/5 of nucleus size and is located near it. The appearance of MN is a natural process of the organism that occurs with aging itself, but exposure to xenobiotics and some diseases can increase the frequency resulting in DNA damage (Sommer et al. 2020). Comet assay (SCEG) is a method that quantifies DNA breakage. It consists in the movement of DNA fragments when subjected to electrophoresis. The lower molecular weight fragments are dragged in the anionic direction, resulting in a comet shape. The length of the tail determines the damage to the genetic material (Lu et al. 2017; Møller et al. 2020). There are two types of comet assay. The most specific is the alkaline one for detecting damage in single strands, double strands, incomplete repair regions and alkali-labile. Neutral comet assay only detects double-stranded DNA damage (Singh 2016). The sister chromatid exchange (SCE) test is able to determine the impact of clastogens effects on whole chromosomes. During the S phase of the cell cycle, occurs crossing over of genetic material between two chromatids in the same chromosome. Exposure to a genotoxic compound can lead to an increase in SCE. This technique evaluates DNA damage quantitatively and qualitatively (Wilson Iii and Thompson 2007; Kwasniewska and Bara 2020). Chromosomal aberration (ABS) test is used to identify toxic substances with the potential to induce abnormalities to chromosomes, such as chromosomal breaks or translocation of sister chromatids and thereby result in damage to genetic material, mutations, and cancer (Turkez et al. 2017).