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For the purpose of forming cells possessing more than three nuclei and of determining the factors inducing multinucleation, cells of Saccharomyces cerevisiae were treated with 0, 0.3, 0.5, and 1.0%, [w/v] colchicine solution, with...
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For the purpose of forming cells possessing more than three nuclei and of determining the factors inducing multinucleation, cells of Saccharomyces cerevisiae were treated with 0, 0.3, 0.5, and 1.0%, [w/v] colchicine solution, with and without shaking. When the cells were treated with 1.0% [w/v] colchicine solution, the number of cells containing two to eight nuclei was the largest. The multinucleate cells could grow on potato dextrose agar medium and their multinucleate nature did not disappear for at least three generations. This means that such cells an genetically stable. The proliferation rate of the multinucleate cells was not superior to that of the original strain. However, by monitoring the weight loss of the flask, it was possible to indirectly estimate the increase in the alcohol production of the multinucleate cell. It was concluded that the shaking treatment and higher colchicine concentrations contributed to multinucleation.
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Carcinogens, such as benzo[a]pyrene (B[a]P), allow cells to evade G(1) arrest (the stealth property), thus increasing the chance that DNA damage will ultimately result in transformation. In this study we have investigated the effe...
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Carcinogens, such as benzo[a]pyrene (B[a]P), allow cells to evade G(1) arrest (the stealth property), thus increasing the chance that DNA damage will ultimately result in transformation. In this study we have investigated the effects of B[a]P in MCF-7 cells incubated in the presence or absence of oestrogens (beta-oestradiol, oestrone or oestriol). The cytokinesis block micronucleus assay was used to examine cells for chromosomal damage. Micronuclei were scored in 500 binucleate cells per treatment. Increased micronucleus formation (3-fold) occurred following 24 h treatment with 10(-6) M B[a]P alone. Following co-treatment with either 10(-9) M beta-oestradiol, 10(-8) M oestrone or 10(-8) M oestriol, 2- to 3-fold increases in micronuclei were observed with 10(-8) M B[a]P. When MCF-7 cells were pre-incubated for 96 h with 10(-9) M beta-oestradiol, 10(-8) M oestrone or 10(-8) M oestriol prior to the addition of B[a]P for 24 h, up to a 5-fold enhanced sensitivity to micronucleus formation was observed with beta-oestradiol and oestrone, while oestriol appeared to reduce levels of micronucleus formation. B[a]P-induced decreases in cell proliferation (per cent binucleate cells) and plating efficiency were reversed by all three oestrogens. Analysis of cell cycle distributions revealed that treatment with oestrogens or B[a]P alone did not induce marked effects on cell cycle distributions. However, in combination oestrogen and B[a]P induced increases in G(0)/G(1), decreases in S phase and increases in G(2)/M. This work suggests that whilst oestrogens appear to enhance carcinogen-induced DNA damage, they also appear, paradoxically, to trigger mechanisms that facilitate clonogenic survival, which may be relevant to breast cancer initiation.
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The formation of a micronucleus due to chromosome lagging is a well known mechanism of chromosomal loss. However, the post-mitotic fate of the micronucleus and the chromosomal DNA within it is poorly understood. We observed micron...
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The formation of a micronucleus due to chromosome lagging is a well known mechanism of chromosomal loss. However, the post-mitotic fate of the micronucleus and the chromosomal DNA within it is poorly understood. We observed micronuclei (MN) that had multiple copies of the X chromosome (ranging from 4 to 10) when analyzing cultured human lymphocytes using fluorescence in situ hybridization (FISH). A possible mechanism for this observation is that the chromosome(s) or chromatid(s) contained within the micronuclei successfully completed one or more cycles of replication after their expulsion from the primary nucleus.
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The nucleoside reverse transcriptase inhibitor zidovudine (AZT) induces genotoxic damage that includes centrosomal amplification (CA>2 centrosomes/cell) and micronucleus (MN) formation. Here we explored these end points in mice de...
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The nucleoside reverse transcriptase inhibitor zidovudine (AZT) induces genotoxic damage that includes centrosomal amplification (CA>2 centrosomes/cell) and micronucleus (MN) formation. Here we explored these end points in mice deficient in DNA repair and tumor suppressor function to evaluate their effect on AZT-induced DNA damage. We used mesenchymal-derived fibroblasts cultured from C57BL/6J mice that were null and wild type (WT) for Xpa, and WT, haploinsufficient and null for p53 (6 different genotypes). Dose-responses for CA formation, in cells exposed to 0, 10, and 100 M AZT for 24 hr, were observed in all genotypes except the Xpa((+/+))p53((+/-)) cells, which had very low levels of CA, and the Xpa((-/-))p53((-/-)) cells, which had very high levels of CA. For CA there was a significant three-way interaction between Xpa, p53, and AZT concentration, and Xpa((-/-)) cells had significantly higher levels of CA than Xpa((+/+)) cells, only for p53((+/-)) cells. In contrast, the MN and MN+chromosomes (MN+C) data showed a lack of AZT dose response. The Xpa((-/-)) cells, with p53((+/+)) or ((+/-)) genotypes, had levels of MN and MN+C higher than the corresponding Xpa((+/+)) cells. The data show that CA is a major event induced by exposure to AZT in these cells, and that there is a complicated relationship between AZT and CA formation with respect to gene dosage of Xpa and p53. The loss of both genes resulted in high levels of damage, and p53 haploinsufficicency strongly protected Xpa((+/+)) cells from AZT-induced CA damage. Environ. Mol. Mutagen. 55:719-726, 2014. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
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The detection of aneugenic chemicals is important due to the implications of aneuploidy for human health. Aneuploidy can result from chromosome loss or nondisjunction due to chromosome mis-segregation at anaphase. Frequently, aneu...
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The detection of aneugenic chemicals is important due to the implications of aneuploidy for human health. Aneuploidy can result from chromosome loss or nondisjunction due to chromosome mis-segregation at anaphase. Frequently, aneugens are detected using the in vitro micronucleus assay (IVM), with either centromere or kinetochore labeling. However, this method does not consider nondisjunction, the suggested predominant mechanism of spindle poison induced aneugenicity in primary human lymphocytes. Therefore, the IVM may be relatively insensitive in detecting aneuploidy. To investigate whether chromosome distribution analysis, specifically of nondisjunction, using chromosome-specific centromeric probes provides a more sensitive assay for aneugen detection, six reference aneugens with differing modes of action were tested on human lymphoblastoid TK6 cells. The results show that chromosome loss is a substantial part of the process leading to aneuploidy in TK6 cells. This differs from previous studies on human lymphocytes where nondisjunction has been described as the major mechanism of aneugenicity. However, in the current study more cells and types of aneugenic damage were analyzed. Although compound specific effects on nondisjunction were identified, chromosome distribution analysis did not provide increased sensitivity for the detection of aneugens: For the six reference aneugens examined, chromosome loss was shown at the same concentrations or lower than nondisjunction, even when nondisjunction levels were comparatively high. Therefore, in TK6 cells methods that detect chromosome loss, eg, the IVM, provide a more sensitive technique for the detection of aneugens than the measurement of nondisjunction.
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BACKGROUND :Many of the contents of cigarette smoke are genotoxic in nature, and consequently, cytogenetic injury seems to be a trustworthy biomarker for deciding the influence of exposure to chromosome damaging agents in smoke. T...
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BACKGROUND :Many of the contents of cigarette smoke are genotoxic in nature, and consequently, cytogenetic injury seems to be a trustworthy biomarker for deciding the influence of exposure to chromosome damaging agents in smoke. The cytokinesis-block micronucleus assay (CBMN assay) has been proven to be an effectual tool for the study of micronuclei (MN) that will help in estimating the genotoxicity in tobacco users alone which will further help in early cancer detection. OBJECTIVE :The objective is to find out whether there is pronounced contrast in genotoxicity between tobacco users and nonusers by determining MN number in peripheral blood lymphocytes using CBMN assay. METHODOLOGY :MN frequency in peripheral blood lymphocytes was estimated in 5 ml of fresh blood obtained from sixty individuals using tobacco either smoking, chewing, or combination of both and also from thirty individuals with no habit of tobacco use. All were in the age group of 20-40 years. RESULTS :There was a significant increase in genotoxicity in tobacco users when compared to that of nontobacco users. A positive correlation was also obtained between smoking index and MN frequency in the study. CONCLUSION :Approximation of frequency of MN by CBMN assay can be used to evaluate the genotoxicity present in blood and helps in identifying tobacco users who are at a high risk for the presence of cancer even before the appearance of clinical changes. Copyright: ? 2021 Journal of Pharmacy and Bioallied Sciences.
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Micronucleus experiments are mutagenicity-testing systems used to identify chemicals and pollutants that cause DNA particles to change, such as micronuclei in the cytoplasm of Interphase cells. Damage caused by genotoxic pollutant...
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Micronucleus experiments are mutagenicity-testing systems used to identify chemicals and pollutants that cause DNA particles to change, such as micronuclei in the cytoplasm of Interphase cells. Damage caused by genotoxic pollutants on DNA is the first effect that occurs in aquatic organisms. This paper reported that the micronucleus test gives sensible results in monitoring the chemical and anthropogenic pollution.
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Abstract Objective Resveratrol (RSV) a medicinal polyphenol is synthesized by many plants in response to injury, infection, stress, and ultraviolet (UV) irradiation, present in the grapes, nuts, fruits, and wine. Methods In this s...
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Abstract Objective Resveratrol (RSV) a medicinal polyphenol is synthesized by many plants in response to injury, infection, stress, and ultraviolet (UV) irradiation, present in the grapes, nuts, fruits, and wine. Methods In this study, we have investigated the antioxidant ability of RSV and its activity in the protection of radiation-induced DNA injury in X-radiated mice. The antioxidant strength of RSV was evaluated by the study of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging properties. Results Our results demonstrated that RSV shows strong antioxidant activity by this assay. When mice were exposed to 2?Gy X-radiation, there was an increase in the total MnPCE value and a decrease in the ratio [PCEs/ (PCEs + NCEs)] of bone marrow cells. RSV (50?mg/kg) pretreatment remarkably decreased the total MnPCE value and increased the ratio [PCEs/ (PCEs + NCEs)] in irradiated mice. Conclusions These results propose that RSV protects X-radiation-induced DNA damage in mice bone marrow cells, which may be related to its antioxidant activity.
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The present study was conducted to study genotoxic effect of excessive exposure to cadmium, lead and their mixture in Wistar rats. Sixty colony bred albino Wistar rats were divided randomly into five groups. The rats of group I re...
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The present study was conducted to study genotoxic effect of excessive exposure to cadmium, lead and their mixture in Wistar rats. Sixty colony bred albino Wistar rats were divided randomly into five groups. The rats of group I received only deionisedwater and served as negative control while, group II, III and IV were orally gavaged with cadmium chloride @ lOOppm; lead acetate @ 500 ppm; and mixture of cadmium chloride @ lOOppm & lead acetate @ 500ppm respectively for 28 days. Group V was kept as apositive control, and was given cycophosphamide (20 mg/kg body weight i.p. 24 hours prior to terminal sacrifice). All the three treatment groups showed significant (PO.05) increase in micronuclei as compared to negative control. The findings of the micronuclei study suggested that cadmium and lead when administered alone were equally genotoxic to that of mixture of both the metals at the given dose level however their genotoxic potential was less than the positive control.
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Micronuclei are extra-nuclear bodies containing whole chromosomes that were not incorporated into the nucleus after cell division or damaged chromosome fragments. Even though the link between micronuclei and DNA damage is describe...
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Micronuclei are extra-nuclear bodies containing whole chromosomes that were not incorporated into the nucleus after cell division or damaged chromosome fragments. Even though the link between micronuclei and DNA damage is described for a long time, little is known about the functional organization of micronuclei and their contribution to tumorigenesis. We showed fusions between micronuclear membranes and lysosomes by electron microscopy and linked lysosome function to DNA damage levels in micronuclei. In addition, micronuclei drastically differ from primary nuclei in nuclear envelope composition, with a significant increase in the relative amount of nuclear envelope proteins LBR and emerin and a decrease in nuclear pore proteins. Strikingly, micronuclei lack active proteasomes, as the processing subunits and other factors of the ubiquitin proteasome system. Moreover, micronuclear chromatin shows a higher degree of compaction as compared to primary nuclei. The specific aberrations identified in micronuclei and the potential functional consequences of these defects may contribute to the role of micronuclei in catastrophic genomic rearrangements.
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