Experimental Antioxidant Therapy in Ataxia Telangiectasia
Ataxia telangiectasia (AT) is a rare genetic disorder characterized by immunodeficiency, early onset neurological degeneration, hypersensitivity to ionizing radiation and a high incidence of lymphoid cancers. The disease results from bi-allelic mutations in the AT mutated ( ATM ) gene involved in ce...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2008-01-01
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| Series: | Clinical Medicine Insights: Oncology |
| Online Access: | https://doi.org/10.4137/CMO.S535 |
| _version_ | 1818513743052537856 |
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| author | Ramune Reliene Robert H. Schiestl |
| author_facet | Ramune Reliene Robert H. Schiestl |
| author_sort | Ramune Reliene |
| collection | DOAJ |
| description | Ataxia telangiectasia (AT) is a rare genetic disorder characterized by immunodeficiency, early onset neurological degeneration, hypersensitivity to ionizing radiation and a high incidence of lymphoid cancers. The disease results from bi-allelic mutations in the AT mutated ( ATM ) gene involved in cell cycle checkpoint control and repair of DNA double-strand breaks. Evidence has been accumulating that oxidative stress is associated with AT and may be involved in the pathogenesis of the disease. This led to a hypothesis that antioxidant therapy may mitigate the symptoms of AT, especially neurological degeneration and tumorigenesis. Consequently, several studies examined the effect of antioxidants in Atm deficient mice used as an animal model of AT. N-acetyl-L-cysteine (NAC), EUK-189, tempol and 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) have been tested for their chemopreventive properties and had some beneficial effects. In addition to antioxidants, cancer therapeutic agent dexamethasone was examined for cancer prevention in Atm deficient mice. Of the tested antioxidants, only NAC has wide clinical applications due to safety and efficacy and is available as an over-the-counter dietary supplement. In this article, we review chemoprevention studies in Atm deficient mice and, in more detail, our findings on the effect of NAC. The short-tem study showed that NAC suppressed genome rearrangements linked to cancer. The long-term study demonstrated that NAC reduced both the incidence and multiplicity of lymphoma. |
| first_indexed | 2024-12-11T00:05:48Z |
| format | Article |
| id | doaj.art-2d9b686a60244c459f07adf1789fb863 |
| institution | Directory Open Access Journal |
| issn | 1179-5549 |
| language | English |
| last_indexed | 2024-12-11T00:05:48Z |
| publishDate | 2008-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical Medicine Insights: Oncology |
| spelling | doaj.art-2d9b686a60244c459f07adf1789fb8632022-12-22T01:28:19ZengSAGE PublishingClinical Medicine Insights: Oncology1179-55492008-01-01210.4137/CMO.S535Experimental Antioxidant Therapy in Ataxia TelangiectasiaRamune Reliene0Robert H. Schiestl1Department of Medicine, Center for Human Nutrition, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, U.S.A.Department of Environmental Health, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, U.S.A.Ataxia telangiectasia (AT) is a rare genetic disorder characterized by immunodeficiency, early onset neurological degeneration, hypersensitivity to ionizing radiation and a high incidence of lymphoid cancers. The disease results from bi-allelic mutations in the AT mutated ( ATM ) gene involved in cell cycle checkpoint control and repair of DNA double-strand breaks. Evidence has been accumulating that oxidative stress is associated with AT and may be involved in the pathogenesis of the disease. This led to a hypothesis that antioxidant therapy may mitigate the symptoms of AT, especially neurological degeneration and tumorigenesis. Consequently, several studies examined the effect of antioxidants in Atm deficient mice used as an animal model of AT. N-acetyl-L-cysteine (NAC), EUK-189, tempol and 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) have been tested for their chemopreventive properties and had some beneficial effects. In addition to antioxidants, cancer therapeutic agent dexamethasone was examined for cancer prevention in Atm deficient mice. Of the tested antioxidants, only NAC has wide clinical applications due to safety and efficacy and is available as an over-the-counter dietary supplement. In this article, we review chemoprevention studies in Atm deficient mice and, in more detail, our findings on the effect of NAC. The short-tem study showed that NAC suppressed genome rearrangements linked to cancer. The long-term study demonstrated that NAC reduced both the incidence and multiplicity of lymphoma.https://doi.org/10.4137/CMO.S535 |
| spellingShingle | Ramune Reliene Robert H. Schiestl Experimental Antioxidant Therapy in Ataxia Telangiectasia Clinical Medicine Insights: Oncology |
| title | Experimental Antioxidant Therapy in Ataxia Telangiectasia |
| title_full | Experimental Antioxidant Therapy in Ataxia Telangiectasia |
| title_fullStr | Experimental Antioxidant Therapy in Ataxia Telangiectasia |
| title_full_unstemmed | Experimental Antioxidant Therapy in Ataxia Telangiectasia |
| title_short | Experimental Antioxidant Therapy in Ataxia Telangiectasia |
| title_sort | experimental antioxidant therapy in ataxia telangiectasia |
| url | https://doi.org/10.4137/CMO.S535 |
| work_keys_str_mv | AT ramunereliene experimentalantioxidanttherapyinataxiatelangiectasia AT roberthschiestl experimentalantioxidanttherapyinataxiatelangiectasia |