Oxidation-Mediated DNA Crosslinking Contributes to Toxicity of 6-Thioguanine in Human Cells — Letter
نویسندگان
چکیده
منابع مشابه
Oxidation-mediated DNA cross-linking contributes to the toxicity of 6-thioguanine in human cells.
The thiopurines azathioprine and 6-mercaptopurine have been extensively prescribed as immunosuppressant and anticancer agents for several decades. A third member of the thiopurine family, 6-thioguanine (6-TG), has been used less widely. Although known to be partly dependent on DNA mismatch repair (MMR), the cytotoxicity of 6-TG remains incompletely understood. Here, we describe a novel MMR-inde...
متن کاملCrosslinking of DNA repair and replication proteins to DNA in cells treated with 6-thioguanine and UVA
The DNA of patients taking immunosuppressive and anti-inflammatory thiopurines contains 6-thioguanine (6-TG) and their skin is hypersensitive to ultraviolet A (UVA) radiation. DNA 6-TG absorbs UVA and generates reactive oxygen species that damage DNA and proteins. Here, we show that the DNA damage includes covalent DNA-protein crosslinks. An oligonucleotide containing a single 6-TG is photochem...
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The structural maintenance of chromosomes (SMC) proteins constitute the core of critical complexes involved in structural organization of chromosomes. In yeast, the Smc5/6 complex is known to mediate repair of DNA breaks and replication of repetitive genomic regions, including ribosomal DNA loci and telomeres. In mammalian cells, which have diverse genome structure and scale from yeast, the Smc...
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6-Thioguanine (isG) has been used for the past thirty years as an anti-cancer agent in maintenance chemotherapy for childhood acute lymphoblastic leukemia as well as acute myeloid leukemia. Despite its long-standing clinical use, little is understood of the molecular basis of the cytotoxicity associated with 6SG. Research has shown that 6SG is incorporated into DNA during replication after whic...
متن کاملMUTYH mediates the toxicity of combined DNA 6-thioguanine and UVA radiation
The therapeutic thiopurines, including the immunosuppressant azathioprine (Aza) cause the accumulation of the UVA photosensitizer 6-thioguanine (6-TG) in the DNA of the patients' cells. DNA 6-TG and UVA are synergistically cytotoxic and their interaction causes oxidative damage. The MUTYH DNA glycosylase participates in the base excision repair of oxidized DNA bases. Using Mutyh-nullmouse fibro...
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ژورنال
عنوان ژورنال: Cancer Research
سال: 2013
ISSN: 0008-5472,1538-7445
DOI: 10.1158/0008-5472.can-12-3120