Cells Deficient in the FANC/BRCA Pathway Are Hypersensitive to Plasma Levels of Formaldehyde
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- John R. Ridpath
- 1Department of Environmental Sciences and Engineering, and
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- Ayumi Nakamura
- 1Department of Environmental Sciences and Engineering, and
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- Keizo Tano
- 4Research Reactor Institute, Kyoto University, Kumatori, Japan;
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- April M. Luke
- 2Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
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- Eiichiro Sonoda
- 5Department of Radiation Genetics Graduate School of Medicine, Kyoto, Japan;
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- Hiroshi Arakawa
- 6GSF-National Research Center for Environment and Health, Institute for Molecular Radiobiology, Neuherberg-Munich, Germany;
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- Jean-Marie Buerstedde
- 6GSF-National Research Center for Environment and Health, Institute for Molecular Radiobiology, Neuherberg-Munich, Germany;
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- David A.F. Gillespie
- 7Beatson Institute for Cancer Research, Glasgow, United Kingdom;
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- Julian E. Sale
- 8Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, United Kingdom;
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- Mitsuyoshi Yamazoe
- 5Department of Radiation Genetics Graduate School of Medicine, Kyoto, Japan;
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- Douglas K. Bishop
- 9Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois; and
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- Minoru Takata
- 10Department of Human Genetics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
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- Shunichi Takeda
- 5Department of Radiation Genetics Graduate School of Medicine, Kyoto, Japan;
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- Masami Watanabe
- 4Research Reactor Institute, Kyoto University, Kumatori, Japan;
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- James A. Swenberg
- 1Department of Environmental Sciences and Engineering, and
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- Jun Nakamura
- 1Department of Environmental Sciences and Engineering, and
書誌事項
- 公開日
- 2007-12-01
- DOI
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- 10.1158/0008-5472.can-07-3028
- 公開者
- American Association for Cancer Research (AACR)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>Formaldehyde is an aliphatic monoaldehyde and is a highly reactive environmental human carcinogen. Whereas humans are continuously exposed to exogenous formaldehyde, this reactive aldehyde is a naturally occurring biological compound that is present in human plasma at concentrations ranging from 13 to 97 μmol/L. It has been well documented that DNA-protein crosslinks (DPC) likely play an important role with regard to the genotoxicity and carcinogenicity of formaldehyde. However, little is known about which DNA damage response pathways are essential for cells to counteract formaldehyde. In the present study, we first assessed the DNA damage response to plasma levels of formaldehyde using chicken DT40 cells with targeted mutations in various DNA repair genes. Here, we show that the hypersensitivity to formaldehyde is detected in DT40 mutants deficient in the BRCA/FANC pathway, homologous recombination, or translesion DNA synthesis. In addition, FANCD2-deficient DT40 cells are hypersensitive to acetaldehyde, but not to acrolein, crotonaldehyde, glyoxal, and methylglyoxal. Human cells deficient in FANCC and FANCG are also hypersensitive to plasma levels of formaldehyde. These results indicate that the BRCA/FANC pathway is essential to counteract DPCs caused by aliphatic monoaldehydes. Based on the results obtained in the present study, we are currently proposing that endogenous formaldehyde might have an effect on highly proliferating cells, such as bone marrow cells, as well as an etiology of cancer in Fanconi anemia patients. [Cancer Res 2007;67(23):11117–22]</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 67 (23), 11117-11122, 2007-12-01
American Association for Cancer Research (AACR)
