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Mitotic Recombination (mitotic + recombination)
Selected AbstractsGenotoxicity of three mouthwash products, Cepacol®, Periogard®, and Plax®, in the Drosophila wing-spot testENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2007Fábio Rodrigues Abstract Antiseptic mouthwashes used in biofilm control are widely available in the marketplace, despite inconsistent data concerning their genetic and cellular toxicity. In the present study, we investigated the genotoxic potential of three antiseptics currently used for odontologic treatment, Cepacol® (containing cetylpyridinium chloride), Periogard® (chlorhexidine digluconate), and Plax® (triclosan). Genotoxicity was evaluated using the Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster, employing flies having normal bioactivation (the standard cross) and flies with increased cytochrome P450-dependent biotransformation capacity (the high bioactivation cross). Periogard and Plax produced negative responses in both types of flies; however, Cepacol (75 and 100%) produced positive responses in both the standard and high bioactivation assays, with the genotoxic responses mainly due to the induction of mitotic recombination. Assays performed with ethanol and cetylpirydinium chloride, two major ingredients of Cepacol, indicated that the genotoxity of the mouthwash is likely to be due to ethanol. Environ. Mol. Mutagen., 2007. © 2007 Wiley-Liss, Inc. [source] Assessing the impact of pollution on the Japaratuba river in Brazil using the Drosophila wing spot testENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2007Silmara de Moraes Pantaleão Abstract The Drosophila melanogaster somatic mutation and recombination test (SMART) was used to assess the genotoxicity of surface (S) and bottom (B) water and sediment samples collected from Sites 1 and 2 on the Japaratuba River (Sergipe, Brazil), an area impacted by a petrochemical industrial complex that indirectly discharges treated effluent (produced water) into the river. The genotoxicity tests were performed in standard (ST) cross and high bioactivation (HB) cross flies and were conducted on samples taken in March (dry season) and in July (rainy season) of 2003. Mutant spot frequencies found in treatments with unprocessed water and sediment samples from the test sites were compared with the frequencies observed for similar samples taken from a clean reference site (the Jacarecica River in Sergipe, Brazil) and those of negative (ultrapure water) controls. While samples from the Japaratuba River generally produced greater responses than those from the Jacarecica River, positive responses were detected for both the test and reference site samples. All the water samples collected in March 2003 were genotoxic. In July 2003, the positive responses were restricted to water samples collected from Sites 1 B and 2 S in the ST cross. The genotoxicity of the water samples was due to mitotic recombination, and the samples produced similar genotoxic responses in ST and HB flies. The spot frequencies found in the July water samples were considerably lower than those for the March water samples, suggesting a seasonal effect. The only sediment samples that were genotoxic were from Site 1 (March and July) and from the Jacarecica River (March). The genotoxins in these samples produced both somatic mutation (limited to the Site 1 sample in HB flies) and recombination. The results of this study indicate that samples from both the Japaratuba and Jacarecica Rivers were genotoxic, with the most consistently positive responses detected with Site 1 samples, the site closest to the putative pollution source. Environ. Mol. Mutagen. 48:, 2007. © 2007 Wiley-Liss, Inc. [source] Novel regions of acquired uniparental disomy discovered in acute myeloid leukemiaGENES, CHROMOSOMES AND CANCER, Issue 9 2008Manu Gupta The acquisition of uniparental disomy (aUPD) in acute myeloid leukemia (AML) results in homozygosity for known gene mutations. Uncovering novel regions of aUPD has the potential to identify previously unknown mutational targets. We therefore aimed to develop a map of the regions of aUPD in AML. Here, we have analyzed a large set of diagnostic AML samples (n = 454) from young adults (age: 15,55 years) using genotype arrays. Acquired UPD was found in 17% of the samples with a nonrandom distribution particularly affecting chromosome arms 13q, 11p, and 11q. Novel recurrent regions of aUPD were uncovered at 2p, 17p, 2q, 17q, 1p, and Xq. Overall, aUPDs were observed across all cytogenetic risk groups, although samples with aUPD13q (5.4% of samples) belonged exclusively to the intermediate-risk group as defined by cytogenetics. All cases with a high FLT3 -ITD level, measured previously, had aUPD13q covering the FLT3 gene. Significantly, none of the samples with FLT3 -ITD - /FLT3 -TKD+ mutation exhibited aUPD13q. Of the 119 aUPDs observed, the majority (87%) were due to mitotic recombination while only 13% were due to nondisjunction. This study demonstrates aUPD is a frequent and significant finding in AML and pinpoints regions that may contain novel mutational targets. © 2008 Wiley-Liss, Inc. [source] Somatic loss of wild type NF1 allele in neurofibromas: Comparison of NF1 microdeletion and non-microdeletion patientsGENES, CHROMOSOMES AND CANCER, Issue 10 2006Thomas De Raedt Neurofibromatosis type I (NF1) is an autosomal dominant familial tumor syndrome characterized by the presence of multiple benign neurofibromas. In 95% of NF1 individuals, a mutation is found in the NF1 gene, and in 5% of the patients, the germline mutation consists of a microdeletion that includes the NF1 gene and several flanking genes. We studied the frequency of loss of heterozygosity (LOH) in the NF1 region as a mechanism of somatic NF1 inactivation in neurofibromas from NF1 patients with and without a microdeletion. There was a statistically significant difference between these two patient groups in the proportion of neurofibromas with LOH. None of the 40 neurofibromas from six different NF1 microdeletion patients showed LOH, whereas LOH was observed in 6/28 neurofibromas from five patients with an intragenic NF1 mutation (P = 0.0034, Fisher's exact). LOH of the NF1 microdeletion region in NF1 microdeletion patients would de facto lead to a nullizygous state of the genes located in the deletion region and might be lethal. The mechanisms leading to LOH were further analyzed in six neurofibromas. In two out of six neurofibromas, a chromosomal microdeletion was found; in three, a mitotic recombination was responsible for the observed LOH; and in one, a chromosome loss with reduplication was present. These data show an important difference in the mechanisms of second hit formation in the 2 NF1 patient groups. We conclude that NF1 is a familial tumor syndrome in which the type of germline mutation influences the type of second hit in the tumors. © 2006 Wiley-Liss, Inc. [source] Intrinsic genetic instability of normal human lymphocytes and its implication for loss of heterozygosityGENES, CHROMOSOMES AND CANCER, Issue 4 2001Arnolda G. de Nooij-van Dalen A combination of flow cytometry and microsatellite analysis was used to investigate loss of expression of HLA-A and/or HLA-B alleles and concurrent LOH at polymorphic chromosome 6 loci both in freshly isolated lymphocytes (in vivo mutations) and in lymphocytes cultured ex vivo. The fraction of in vivo mutants that showed LOH at 6p appeared to vary from 0%,49% for various donors. During culturing ex vivo, HLA-A, cells arose at a high rate and showed simultaneous loss of expression at the linked HLA-B locus. Up to 90% of the ex vivo arisen HLA-A2, cell population showed LOH of multiple 6p markers, and 50% had lost heterozygosity at 6q. This ex vivo spectrum resembles that found in HLA-A2 mutants obtained from lymphoblastoid cells. The HLA-A2 mutants present in vivo may reflect only a small fraction of the mutants that can be detected ex vivo. In normal lymphocytes, in vivo only mitotic recombination appears to be sustained, indicating the importance of this mechanism for tumor initiation in normal cells. Although mutations resulting in LOH at both chromosome 6 arms were shown to result in nonviable cells in normal lymphocytes, they have been shown to result in viable mutants in lymphoblastoid cells. We hypothesize that these types of mutations also occur in vivo but only survive in cells that already harbor a mutated genetic background. In light of the high rate at which these types of mutations occur, they may contribute to cancer progression. © 2001 Wiley-Liss, Inc. [source] Liver carcinogen aflatoxin B1 as an inducer of mitotic recombination in a human cell lineMOLECULAR CARCINOGENESIS, Issue 3 2001Peter Markus Stettler Abstract The mycotoxin aflatoxin B1 (AFB1) is one of the most potent rodent and human liver carcinogens. Upon cytochrome P450,specific metabolism, it induces mutations as well as mitotic recombination events in in vitro systems. We have found that in the lower eukaryote yeast, the recombinagenic activity of AFB1 surpasses its mutagenic activity, and we speculated on possible consequences in terms of the mechanism of liver carcinogenesis. In this study we investigated whether the recombinagenic activity of AFB1 also would be identified in human cells. To address this question, we followed the fate of a heterozygous thymidine kinase (tk) allele in the human lymphoblastoid cell line TK6 upon exposure to AFB1. Individual mutants that had lost tk activity were subjected to loss of heterozygosity analysis of the tk locus and its flanking markers. Fluorescence in situ hybridization analysis on chromosome 17 also was performed. In parallel, a similar analysis was performed on TK6 cells exposed to the alkylating agent N -nitrosomethylurea, a well-known classic point mutagen. Our analysis showed a difference in the molecular mechanism leading to inactivation of the tk allele upon exposure to these two mutagens. In AFB1 -exposed cells the fraction of recombination-derived mutants predominated, whereas in N -nitrosomethylurea,exposed cells the fraction of point mutants was higher. Thus, the recombinagenic activity of AFB1 previously identified in a lower eukaryote also was found in the human cell line TK6. Our data support the hypothesis that mitotic recombination represents a central mechanism of action in AFB1 -induced liver carcinogenesis. © 2001 Wiley-Liss, Inc. [source] Chemistry and genotoxicity of caramelized sucroseMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 12 2006David D. Kitts Abstract Caramelization of a 1% sucrose solution at 180°C accompanied characteristic changes in pH, Mr, UV-absorbance, and fluorescence values as well as increased reducing power activity after 40,60 min. Similar changes occurred to sucrose heated at 150°C, after 150,240 min. Bioactivity of caramelized sucrose samples was tested for mutagenic activity, using Salmonella typhimurium strains TA-98 and TA-100, respectively, as well as the Saccharomyces D7 yeast strain for mitotic recombination and Chinese hamster ovary cells (CHO) to assess clastogenicity. Caramelized sucrose expressed no mutagenicity in the TA-98 strain, but gave positive (p < 0.05) results with the TA-100, base-pair substitution strain. Similarly, mitotic recombination in the Saccharomyces D7 yeast strain and clastogenic activity in CHO cells were induced when exposed to caramelized sucrose. In the all cases, preincubation with S-9 reduced (p < 0.05) the mutagenic activities of caramelized sucrose. Fractionation of the caramelized sucrose into volatile and nonvolatile compounds was performed and tested for clastogenicity using CHO cells. Volatile components contributed approximately 10% to total clastogenicity, which was enhanced by the presence of S-9. Nonvolatile components recovered, consisting of relatively lower Mr, gave highest (p < 0.05) clastogenic activity, denoting that higher Mr caramel colors are relatively free of this property. [source] Genetic Toxicology of Dental Composite Resin Extracts in Somatic Cells In VivoBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2010Guilherme Anziliero Arossi Homologous mitotic recombination, point and chromosomal mutation effects were determined in somatic proliferative cells of Drosophila melanogaster exposed to aqueous extracts of the clinically used composites. Reproducible increases in clone mutant spot frequencies induced by diluted extract of Fill Magic Flow were observed. These increments were exclusively associated to the induction of homologous recombination , a genetic phenomenon involved in the loss of heterozygosis. The other eight composite resins and the random extract had no statistically significant effect on total spot frequencies , suggesting that they are non-genotoxic in the somatic mutation and recombination test assay, which agrees with the applications they have in dentistry. These findings , supported by numerous studies showing a positive correlation between carcinogenicity in man and genotoxicity in the Drosophila wing spot test , point to the potential risks some composite resins pose to the health of patients and dentistry personnel. [source] | |||||||||||||