China
Africa
Explore chapters and articles related to this topic
The Molecular Genetics OF DNA Methylation in Colorectal Cancer
Published in Leonard H. Augenlicht, Cell and Molecular Biology of Colon Cancer, 2019
5-azaCR and 5-azaCdR may be transformed by mechanisms not including DNA methylation. For example, 5-azaCR is clastogenic, inducing chromosomal breaks and rearrangements,59 and treatment of normal human cells by 5-azaCR causes decondensation of centromeric heterochromatin with subsequent chromatid interchanges.60 A possible direct chromosomal role of 5-azaCR on transformation is suggested by studies of the hamster cell line CHEF/18. In every case, 5-azaCR-induced transformation of those cells is associated with an abnormality of hamster chromosome 3.61 Point mutation by 5-azaCR is also possible but seems less likely, because the measured frequency of point mutation is several orders of magnitude lower than the transformation frequency.62
Incapacitating Agents and Technologies: A Review *
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
PAVA has a moderate degree of percutaneous absorption in the rabbit: 50–70% over 14 h when applied occlusively as an ointment in oil–water emulsion (Fang et al., 1996). More limited absorption was reported for the rat (12% over 72 hours) using phosphate buffered saline under nonoccluded conditions (Kasting et al., 1997). However, in vitro rat skin permeability studies demonstrated that PAVA in 50% ethanol was absorbed more rapidly than when dissolved in phosphate buffered saline (Kasting et al., 1997). Following absorption, PAVA is extensively metabolized and rapidly excreted; the main route of metabolism is by hydrolytic cleavage of the amide bond with some aliphatic hydroxylation (Kasting et al., 1997;Suhr et al., 1995). There are no detailed published reports on the reproductive toxicity of PAVA. A developmental toxicity study was conducted by gavage in rats (Knox and McKenzie, 2003). Time-mated animals were given doses of 0, 100, 500, and 1000 mg kg−1 day−1 over gestational days 5–19. Maternal toxicity was not noted. Fetal body weights were statistically significantly reduced at 100 mg kg−1 day−1. There were no effects on viability, gender ratio, or visceral and skeletal abnormalities. Studies on the genotoxicity of PAVA are as follows (COT, 2002). In vitro, bacterial reverse mutation assays were negative, a mouse lymphoma test was weakly positive, and a CHO chromosome aberration test was positive at concentrations that were not cytotoxic. In vivo, a bone marrow micronucleus test showed no evidence for clastogenic potential.
In Vitro Methods: Alternatives to Animal Testing
Published in Heather A.E. Benson, Michael S. Roberts, Vânia Rodrigues Leite-Silva, Kenneth A. Walters, Cosmetic Formulation, 2019
Dayane Pifer Luco, Vânia Rodrigues Leite-Silva, Heather A.E. Benson, Patricia Santos Lopes
At least three test concentrations that meet the acceptability criteria (appropriate cytotoxicity, number of cells, etc.) should be evaluated. A cytokinesis blocker (cytochalasin B [cytoB]) may also be included. S9 fraction (an exogenous metabolic activation system containing cytosol and microsomes) is added to activate metabolism in cells, although the exogenous metabolic activation system does not entirely mimic in vivo conditions (OECD 487, 2014). It is mandatory to include clastogenic and aneugenic positive controls, with and without metabolic activation, as well as negative controls, to demonstrate both the ability of the laboratory to identify clastogens and aneugens under the conditions of the test protocol used, and the effectiveness of the exogenous metabolic activation system. Micronuclei in interphase cells can be assessed objectively (Figure 26.3), therefore the slides can be scored relatively quickly and analysis can be automated. This makes it practical to score thousands of cells per treatment, increasing the power of the test.
Cadmium exposure and DNA damage (genotoxicity): a systematic review and meta-analysis
Published in Critical Reviews in Toxicology, 2022
Raju Nagaraju, Ravibabu Kalahasthi, Rakesh Balachandar, Bhavani Shankara Bagepally
Further, Cd exposure induces DNA damage through the DNA metal interaction, oxidative stress, and inhibition of the DNA repair process, epigenetic mechanisms of gene expression control, and interference with cell proliferation (cell cycle checkpoints), differentiation, and apoptosis (Waisberg et al. 2003; Bertin and Averbeck 2006; Viau et al. 2008; Pereira et al. 2013). According to the studies, Cd exposure can potentially be a co-mutagen in vitro and mutagen in vivo system (Hartwig et al. 2002). Furthermore, Cd exposure affects zinc finger proteins, which increases tumor promoters even at low concentrations (Xu et al. 2017). Cd exposure alone acts as a strong mutagen and clastogen at physiological concentration, and this is potentially alarming and could influence the current standards and permissible limits in occupational settings (Ostoich et al. 2020). This results in a probability of developing cancer and other diseases associated with genomic instability (Filipič 2012). Considering the above review of the literature and based on the severity of Cd effects at physiological levels, we compared the effects of occupational Cd exposure on biomarkers of genotoxicity among exposed and unexposed groups in the current study.
Toxicity, preparation methods and applications of silver nanoparticles: an update
Published in Toxicology Mechanisms and Methods, 2022
Anuj Choudhary, Sanjiv Singh, V. Ravichandiran
Widely used test to check out the chromosomal abnormalities by silver nanoparticles. A specific term is used for an agent that causes chromosome abnormalities is clastogen. Chromosomal abnormalities (C.A.) are classified into two categories first is structural and second numerical. Structural abnormalities are further subdivided into four types – deletion, duplication, inversion, translocation. Numerical C.A. is also subdivided into two types – aneuploidy and euploidy. Chromosomal abnormalities depend upon the duration of exposure and amount of silver nanoparticles. To determine chromosomal loss chromosome aberration test can be performed in an invitro and in-vivo way. The procedure of chromosomal aberration involves blockage of cell cycles of cultured mammalian cells with silver nanoparticles at the stage when chromosomes line up on the central plane of the cell i.e., metaphase. The arrested metaphase stage cell is then transferred to the stained with 4–5% Giemsa in phosphate buffer ph around 6.8 for ¼ of the hour. To analyze chromosomal abnormalities with its category then microscope study performed (Galloway et al. 1987).
Exploring graphene-based materials’ genotoxicity: inputs of a screening method
Published in Nanotoxicology, 2021
Salma Achawi, Ludovic Huot, Fabrice Nesslany, Jérémie Pourchez, Sophie Simar, Valérie Forest, Bruno Feneon
Briefly, aneugenicity, clastogenicity or mutagenicity are major genotoxicity mechanisms. For aneugenicity, genotoxicants act primarily on non-DNA targets (microtubule, centrosome or kinetochore (More et al. 2021)) or cause damage to the mitosis apparatus, leading to improper chromosome segregation (Parry et al. 1996, 2002). For clastogenicity, structural chromosome aberrations such as chromatid/chromosome breaks occur (Bignold 2009). Clastogenic agents can covalently bind to DNA or enzymes, leading to chromosome breakage. Mutagenicity corresponds to the induction of DNA mutations (Kumar et al. 2018), either by direct interaction with DNA or chromatin or by indirect mechanisms, such as through generation of reactive oxygen species or inflammation (DeMarini 2019). Genotoxicity is associated to serious health effects, the first one being cancer (Phillips and Arlt 2009): some genotoxic agents can indeed cause mutations that can eventually lead to malign tumor. Hence, most carcinogenic chemicals are genotoxic (Hayashi 1992), which make the measurement of this endpoint critical for hazard assessment.