Home About us Contact
|
Home About us Contact | ||
|
|
||
Micronucleus Formation (micronucleu + formation)
Selected AbstractsArsenate and dimethylarsinic acid in drinking water did not affect DNA damage repair in urinary bladder transitional cells or micronuclei in bone marrow,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2009Amy Wang Abstract Arsenic is a human skin, lung, and urinary bladder carcinogen, and may act as a cocarcinogen in the skin and urinary bladder. Possible modes of action of arsenic carcinogenesis/cocarcinogenesis include oxidative stress induction and inhibition of DNA damage repair. We investigated the effects of arsenic in drinking water on DNA damage repair in urinary bladder transitional cells and on micronucleus formation in bone marrow. F344 rats were given 100 ppm arsenate [As(V)] or dimethylarsinic acid [DMA(V)] in drinking water for 1 week. The in vivo repair of cyclophosphamide (CP)-induced DNA damage resulting from a single oral gavage of CP, and the in vitro repair of hydrogen peroxide (H2O2)- or formaldehyde-induced DNA damage, resulting from adding H2O2 or formaldehyde into cell medium, were measured by the Comet assay. DMA(V) effects were not observed on either CP-induced DNA damage induction or on DNA repair. Neither DMA(V) nor As(V) increased the H2O2 - or formaldehyde-induced DNA damage, and neither inhibited the repair of H2O2 -induced DNA damage. Neither DMA(V) nor As(V) increased the micronucleus frequency, nor did they elevate micronucleus frequency resulting from CP treatment above the level observed by the treatment with CP alone. These results suggest that arsenic carcinogenesis/cocarcinogenesis in the urinary bladder may not be via DNA damage repair inhibition. To our knowledge this is the first report of arsenic effects on DNA damage repair in the urinary bladder. Environ. Mol. Mutagen. 2009. Published 2009 by Wiley-Liss, Inc. [source] Effect of mangiferin on radiation-induced micronucleus formation in cultured human peripheral blood lymphocytesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005Ganesh Chandra Jagetia Abstract Irradiation causes a variety of lesions in important biomolecules of the cell through generation of free radicals leading to genomic instability. DNA strand breaks, acentric fragments, or defective kinetochores are manifested as micronuclei after the first cell division. Chemicals that can trap free radicals may reduce the deleterious effects of ionizing radiation. Mangiferin (MGN), a glucosylxanthone derived from Mangifera indica (mango), was investigated for its ability to reduce the frequency of radiation-induced micronucleated binucleate cells (MNBNCs) in cultured human peripheral blood lymphocytes (HPBLs). HPBL cultures were pretreated with 0, 5, 10, 20, 50, and 100 ,g/ml of MGN for 30 min before exposure to 3 Gy of 60Co ,-radiation. The maximum decline in radiation-induced micronuclei was observed at a concentration of 50 ,g/ml MGN; thereafter, a nonsignificant elevation in MNBNC frequency was observed at 100 ,g/ml MGN. Since the lowest MNBNC frequency was observed for 50 ,g/ml MGN, dose-response studies were undertaken using this concentration. Irradiation of HPBLs with 0, 1, 2, 3, or 4 Gy of ,-radiation caused a dose-dependent elevation in the MNBNC frequency, while treatment of HPBLs with 50 ,g/ml MGN 30 min before radiation resulted in significant declines in these frequencies. MGN alone did not alter the proliferation index. Irradiation caused a dose-dependent decline in the proliferation index, while treatment of HPBLs with 50 ,/ml MGN significantly elevated the proliferation index in irradiated cells. MGN treatment reduced hydrogen peroxide-induced lipid peroxidation in HPBLs in a concentration-dependent fashion. In cell-free studies, MGN inhibited the induction of ·OH (hydroxyl), O2·, (superoxide), DPPH (1,1-diphenyl-2-picrylhydrazyl), and ABTS·+ (2,2-azino-bis-3-ethyl benzothiazoline-6-sulphonic acid) radicals in a dose-dependent manner. The results of this study indicate that MGN possesses radioprotective properties by suppressing the effects of free radicals. Environ. Mol. Mutagen. 45:000,000, 2005. © 2005 Wiley-Liss, Inc. [source] Alterations in gene expression profiles and the DNA-damage response in ionizing radiation-exposed TK6 cells,,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2005Gregory S. Akerman Abstract Identifying genes that are differentially expressed in response to DNA damage may help elucidate markers for genetic damage and provide insight into the cellular responses to specific genotoxic agents. We utilized cDNA microarrays to develop gene expression profiles for ionizing radiation-exposed human lymphoblastoid TK6 cells. In order to relate changes in the expression profiles to biological responses, the effects of ionizing radiation on cell viability, cloning efficiency, and micronucleus formation were measured. TK6 cells were exposed to 0.5, 1, 5, 10, and 20 Gy ionizing radiation and cultured for 4 or 24 hr. A significant (P < 0.0001) decrease in cloning efficiency was observed at all doses at 4 and 24 hr after exposure. Flow cytometry revealed significant decreases in cell viability at 24 hr in cells exposed to 5 (P < 0.001), 10 (P < 0.0001), and 20 Gy (P < 0.0001). An increase in micronucleus frequency occurred at both 4 and 24 hr at 0.5 and 1 Gy; however, insufficient binucleated cells were present for analysis at the higher doses. Gene expression profiles were developed from mRNA isolated from cells exposed to 5, 10, and 20 Gy using a 350 gene human cDNA array platform. Overall, more genes were differentially expressed at 24-hr than at the 4-hr time point. The genes upregulated (> 1.5-fold) or downregulated (< 0.67-fold) at 4 hr were those primarily involved in the cessation of the cell cycle, cellular detoxification pathways, DNA repair, and apoptosis. At 24 hr, glutathione-associated genes were induced in addition to genes involved in apoptosis. Genes involved in cell cycle progression and mitosis were downregulated at 24 hr. Real-time quantitative PCR was used to confirm the microarray results and to evaluate expression levels of selected genes at the low doses (0.5 and 1.0 Gy). The expression profiles reflect the cellular and molecular responses to ionizing radiation related to the recognition of DNA damage, a halt in progression through the cell cycle, activation of DNA-repair pathways, and the promotion of apoptosis. Environ. Mol. Mutagen., 2005. Published 2005 Wiley-Liss, Inc. [source] Evaluation of genotoxic effects in human leukocytes after in vitro exposure to 1950 MHz UMTS radiofrequency fieldBIOELECTROMAGNETICS, Issue 3 2008O. Zeni Abstract In the present study the third generation wireless technology of the Universal Mobile Telecommunication System (UMTS) signal was investigated for the induction of genotoxic effects in human leukocytes. Peripheral blood from six healthy donors was used and, for each donor, intermittent exposures (6 min RF on, 2 h RF off) at the frequency of 1950 MHz were conducted at a specific absorption rate of 2.2 W/kg. The exposures were performed in a transverse electro magnetic (TEM) cell hosted in an incubator under strictly controlled conditions of temperature and dosimetry. Following long duration intermittent RF exposures (from 24 to 68 h) in different stages of the cell cycle, micronucleus formation was evaluated by applying the cytokinesis block micronucleus assay, which also provides information on cell division kinetics. Primary DNA damage (strand breaks/alkali labile sites) was also investigated following 24 h of intermittent RF exposures, by applying the alkaline single cell gel electrophoresis (SCG)/comet assay. Positive controls were included by treating cell cultures with Mitomycin-C and methylmethanesulfonate for micronucleus and comet assays, respectively. The results obtained indicate that intermittent exposures of human lymphocytes in different stages of cell cycle do not induce either an increase in micronucleated cells, or change in cell cycle kinetics; moreover, 24 h intermittent exposures also fail to affect DNA structure of human leukocytes soon after the exposures, likely indicating that repairable DNA damage was not induced. Bioelectromagnetics 29:177,184, 2008. © 2007 Wiley-Liss, Inc. [source] Effect of coexposure to 50 Hz magnetic fields and an aneugen on human lymphocytes, determined by the cytokinesis block micronucleus assayBIOELECTROMAGNETICS, Issue 3 2003G.R. Verheyen Abstract Interference of 50 Hz extremely low frequency magnetic fields (ELF-MF) with the known aneugen vinblastine (VBL) on micronucleus formation was tested with the in vitro cytokinesis block micronucleus assay in human lymphocyte cultures. Isolated lymphocyte cultures were prepared from 18 individuals. Three groups of quadruplicate cultures from six unrelated individuals were exposed to 50 Hz ELF-MF of background (bkg), 80 and 800 ,T, respectively, during the complete incubation period (72 h). Twenty-four hours after culture initiation, one replicate culture from each individual within each ELF-MF group was exposed to 0, 5, 10, or 15 ng/ml VBL. The isolated lymphocyte cultures were scored for the presence of micronuclei, the nuclear division index (NDI), and apoptosis. As expected, increased VBL concentration resulted in an increased micronucleus and apoptosis frequency and in a decreased NDI. In the presence of VBL, there was a systematic tendency for increased micronucleus and apoptosis frequency in the ELF-MF exposed groups compared to the bkg group. In the absence of VBL, we observed no statistically significant effect of ELF-MF on micronucleus induction or apoptosis frequency, but the NDI was significantly higher in the 800 ,T group compared to the other groups, suggesting an effect of ELF-MF on cell proliferation. An interaction between ELF-MF and VBL on NDI was observed. This interaction reflected the drastic decrease in NDI due to coexposure to VBL. Bioelectromagnetics 24:160,164, 2003. © 2003 Wiley-Liss, Inc. [source] | ||||||||||