Chromosomal aberrations induced by defined DNA double-strand breaks: The origin of achromatic lesions

Harvey, Alison N.; Costa, Nina D.; Savage, John R. K.; Thacker, John

doi:10.1007/bf02721372

Cited by 19 publications

(11 citation statements)

References 24 publications

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“…Thus, free radicals become available to cause DNA damage (15). These mechanisms can lead to "double-strand breaks" that can be visualized as the chromatid gaps observed in the present study (21) and/or give rise to more evident chromosome alterations such as breaks, rearrangements, and so on (22).…”

Section: Resultsmentioning

confidence: 60%

Cytotoxicity and genotoxicity of low doses of mercury chloride and methylmercury chloride on human lymphocytes in vitro

Silva-Pereira

Cardoso

Leite

et al. 2005

Braz J Med Biol Res

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Mercury is a xenobiotic metal that is a highly deleterious environmental pollutant. The biotransformation of mercury chloride (HgCl 2 ) into methylmercury chloride (CH 3 HgCl) in aquatic environments is well-known and humans are exposed by consumption of contaminated fish, shellfish and algae. The objective of the present study was to determine the changes induced in vitro by two mercury compounds (HgCl 2 and CH 3 HgCl) in cultured human lymphocytes. Short-term human leukocyte cultures from 10 healthy donors (5 females and 5 males) were set-up by adding drops of whole blood in complete medium. Cultures were separately and simultaneously treated with low doses (0.1 to 1000 µg/l) of HgCl 2 and CH 3 HgCl and incubated at 37ºC for 48 h. Genotoxicity was assessed by chromosome aberrations and polyploid cells. Mitotic index was used as a measure of cytotoxicity. A significant increase (P < 0.05) in the relative frequency of chromosome aberrations was observed for all concentrations of CH 3 HgCl when compared to control, whether alone or in an evident sinergistic combination with HgCl 2 . The frequency of polyploid cells was also significantly increased (P < 0.05) when compared to control after exposure to all concentrations of CH 3 HgCl alone or in combination with HgCl 2 . CH 3 HgCl significantly decreased (P < 0.05) the mitotic index at 100 and 1000 µg/l alone, and at 1, 10, 100, and 1000 µg/l when combined with HgCl 2 , showing a synergistic cytotoxic effect. Our data showed that low concentrations of CH 3 HgCl might be cytotoxic/genotoxic. Such effects may indicate early cellular changes with possible biological consequences and should be considered in the preliminary evaluation of the risks of populations exposed in vivo to low doses of mercury.

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Section: Resultsmentioning

confidence: 60%

Cytotoxicity and genotoxicity of low doses of mercury chloride and methylmercury chloride on human lymphocytes in vitro

Silva-Pereira

Cardoso

Leite

et al. 2005

Braz J Med Biol Res

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“…Moreover, there is experimental evidence that TEGDMA caused large deletions of DNA sequences (Schweikl and Schmalz, 1999). Deletions in the genome of mammalian cells may result from DNA double-strand breaks, which also lead to chromosomal aberrations (Harvey et al, 1997). Our findings on the mutagenicity of TEGDMA correlate with the activity of tetraethyleneglycol dimethacrylate (Dearfield et al, 1988).…”

Section: Induction Of Micronucleimentioning

confidence: 49%

The Induction of Micronuclei in vitro by Unpolymerized Resin Monomers

2001

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Components of resin materials may damage DNA, leading to genetic alterations in mammalian cells. Here, monomers were analyzed for the induction of chromosomal aberrations indicated by micronuclei induced in V79 cells. A dose-related increase in the numbers of micronuclei was observed with triethyleneglycol dimethacrylate (TEGDMA), 2-hydroxyethyl methacrylate (HEMA), and glycidyl methacrylate (GMA). These effects were reduced, however, by a metabolically active microsomal fraction from rat liver. The very low activity of Bis-GMA and UDMA and the elevated numbers of micronuclei caused by high concentrations of methyl methacrylate and bisphenol A were associated with cytotoxicity. Our findings provide evidence for the induction of micronuclei by TEGDMA, HEMA, and GMA under physiological conditions, indicating clastogenic activity of these chemicals in vitro. Since it has been shown that TEGDMA also caused gene mutations and DNA sequence deletions in mammalian cells, the activity of this substance should be analyzed in vivo.

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“…To test this hypothesis, intact FANCD2 cells and their retroviruscorrected counterparts were electroporated with restriction endonucleases. This treatment has been shown to create chromosomal DNA double strand breaks, ultimately resulting in cell death (31)(32)(33)(34)(35). Fibroblasts were electroporated with the restriction enzyme PvuII, which creates blunt-ended chromosomal double strand breaks.…”

Section: Plasmid End-joining In Intact Wildmentioning

confidence: 99%

A DNA Double Strand Break Repair Defect in Fanconi Anemia Fibroblasts

Donahue

Campbell

2002

Journal of Biological Chemistry

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Fanconi anemia (FA) is a heterogeneous autosomal recessive disease characterized by congenital abnormalities, pancytopenia, and an increased incidence of cancer. Cells cultured from FA patients display elevated spontaneous chromosomal breaks and deletions and are hypersensitive to bifunctional cross-linking agents. Thus, it has been hypothesized that FA is a DNA repair disorder. We analyzed plasmid end-joining in intact diploid fibroblast cells derived from FA patients. FA fibroblasts from complementation groups A, C, D2, and G rejoined linearized plasmids with a significantly decreased efficiency compared with non-FA fibroblasts. Retrovirus-mediated expression of the respective FA cDNAs in FA cells restored their end-joining efficiency to wild type levels. Human FA fibroblasts and fibroblasts from FA rodent models were also significantly more sensitive to restriction enzyme-induced chromosomal DNA double strand breaks than were their retrovirally corrected counterparts. Taken together, these data show that FA fibroblasts have a deficiency in both extra-chromosomal and chromosomal DNA double strand break repair, a defect that could provide an attractive explanation for some of the pathologies associated with FA.

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Chromosomal aberrations induced by defined DNA double-strand breaks: The origin of achromatic lesions

Cited by 19 publications

References 24 publications

Cytotoxicity and genotoxicity of low doses of mercury chloride and methylmercury chloride on human lymphocytes in vitro

Cytotoxicity and genotoxicity of low doses of mercury chloride and methylmercury chloride on human lymphocytes in vitro

The Induction of Micronuclei in vitro by Unpolymerized Resin Monomers

A DNA Double Strand Break Repair Defect in Fanconi Anemia Fibroblasts

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