Induction of micronuclei as a measure of genotoxicity. A Report of the U.S. EPA Gene-Tox Program
Available from: Mary N Mohankumar
- "Cytogenetic biomarkers play a key role in assessing the impact of pollutants in apparently healthy sentinel aquatic organisms such as fishes. Among the cytogenetic end points, the erythrocyte micronucleus assay has gained popularity over other basic cytogenetic assays to assess mutagenic and genotoxic effects of chemicals due to its sensitivity, simplicity, and reliability for detecting cytogenetic DNA damage (Heddle et al. 1983; Al-Sabti and Metcalfe 1995; Cavas and Konen 2007; Bopp et al. 2008; Anbumani and Mohankumar 2012). Pesticides occurring in nature are normally not present individually, but in complex mixtures (Gilliom et al. 2006). "
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ABSTRACT: Cytogenotoxic effects in the form of micronuclei and deformed nucleus, nuclear buds, binucleated cells, vacuolated nucleus, vacuolated cytoplasm, echinocytes, and enucleus induced by two compounds belonging to two different chemical classes of agrochemicals (monocrotophos and butachlor) at sublethal concentrations (0.625, 1.3, and 2.3 ppm and 0.016, 0.032, and 0.064 ppm) in single and combined chronic exposures were studied under laboratory conditions for a period of 35 days in the economically important Indian fish Catla catla. Statistically significant duration-dependent increases in the frequencies of micronucleus (MN) and other cytological anomalies were observed. Compared to single exposures, a twofold increase in micronuclei frequency was noted at combined exposures indicating the synergistic phenomenon. Binucleated and enucleated cells appeared only in fishes exposed to sublethal concentrations of butachlor. The present study is the first of its kind in exploring a significant positive correlation between micronuclei and other nuclear anomalies suggesting them as new possible biomarkers of genotoxicity after agrochemical exposures. The study highlights the sensitivity of the assay in exploring various predictive biomarkers of genotoxic and cytotoxic events and also elicits the synergistic effects of agrochemicals in apparently healthy fishes. C. catla can be considered as a suitable aquatic biomonitoring sentinel species of contaminated water bodies.
Available from: Mohammad Faisal Siddiqui
- "fragments known as micronuclei (MN). These fragments appear in the cytoplasm when the parts of the chromosomes or entire chromosome are not rapidly incorporated in the nuclei of the daughter cells in mitosis because these fragments do not have centromeres; these fragments left behind are incorporated in the secondary nuclei called ''micronuclei'' (Schmid 1975; Heddle et al. 1983). Thus, this test helps to examine the genotoxic effects of contaminants that are present in the aquatic environment (Tucker and Preston 1996). "
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ABSTRACT: The aim of the study was to evaluate the effect of heavy-metal contamination on two fish species (Channa striatus and Heteropneustes fossilis) inhabiting a small freshwater body of northern India. After being captured, each specimen was weighed, measured, and analyzed for heavy metals (chromium [Cr], nickel [Ni], and lead [Pb]). Accumulation of heavy metals was found to be significantly greater (p < 0.05) in different tissues (gill, liver, kidney, and muscle) of fishes captured from the reservoir than from the reference site. Levels of heavy-metal contamination in Shah jamal water was Cr (1.51 mg/l) > Ni (1.22 mg/l) > Pb (0.38 mg/l), which is significantly greater than World Health Organization standards. Bioaccumulation factor was calculated, and it was observed that Pb was most detrimental heavy metal. Condition factor was also influenced. Micronucleus test of fish erythrocytes and comet assay of liver cells confirmed genotoxicity induced by heavy-metal contamination in fishes. Heavy metals (Cr, Ni, and Pb) were increased in both fish species as determined using recommended values of Federal Environmental Protection Agency for edible fishes. This raises a serious concern because these fishes are consumed by the local populations and hence would ultimately affect human health.
Available from: Alexander Shekhtman
- "The assay can detect various types mutations in chromosome 11 including frameshift and base pair substitutions, deletions and translocations . The in vivo rat micronucleus assay measures the number of micronuclei present in polychromatic erythrocytes (PCE) from rat bone marrow , , and is used in determining potential carcinogenicity of compounds and their ability to cause chromosomal damage in replicating cells –. "
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ABSTRACT: AIDS is a global pandemic that has seen the development of novel and effective treatments to improve the quality of life of those infected and reduction of spread of the disease. Palmitic Acid (PA), which we identified and isolated from Sargassum fusiforme, is a naturally occurring fatty acid that specifically inhibits HIV entry by binding to a novel pocket on the CD4 receptor. We also identified a structural analogue, 2-bromopalmitate (2-BP), as a more effective HIV entry inhibitor with a 20-fold increase in efficacy. We have used the structure-activity relationship (SAR) of 2-BP as a platform to identify new small chemical molecules that fit into the various identified active sites in an effort to identify more potent CD4 entry inhibitors. To validate further drug development, we tested the PA and 2-BP scaffold molecules for genotoxic potential. The FDA and International Conference on Harmonisation (ICH) recommends using a standardized 3-test battery for testing compound genotoxicity consisting of the bacterial reverse mutation assay, mouse lymphoma assay, and rat micronucleus assay. PA and 2-BP and their metabolites tested negative in all three genotoxicty tests. 2-BP is the first derivative of PA to undergo pre-clinical screening, which will enable us to now test multiple simultaneous small chemical structures based on activity in scaffold modeling across the dimension of pre-clinical testing to enable transition to human testing.
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