Repair of 3-methyladenine and abasic sites by base excision repair mediates glioblastoma resistance to temozolomide
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چکیده
منابع مشابه
Repair of 3-methyladenine and abasic sites by base excision repair mediates glioblastoma resistance to temozolomide
Alkylating agents have long played a central role in the adjuvant therapy of glioblastoma (GBM). More recently, inclusion of temozolomide (TMZ), an orally administered methylating agent with low systemic toxicity, during and after radiotherapy has markedly improved survival. Extensive in vitro and in vivo evidence has shown that TMZ-induced O(6)-methylguanine (O(6)-meG) mediates GBM cell killin...
متن کاملOvercoming temozolomide resistance in glioblastoma via dual inhibition of NAD+ biosynthesis and base excision repair.
Glioblastoma multiforme (GBM) is a devastating brain tumor with poor prognosis and low median survival time. Standard treatment includes radiation and chemotherapy with the DNA alkylating agent temozolomide (TMZ). However, a large percentage of tumors are resistant to the cytotoxic effects of the TMZ-induced DNA lesion O(6)-methylguanine due to elevated expression of the repair protein O(6)-met...
متن کاملThe role of base excision repair in the sensitivity and resistance to temozolomide-mediated cell death.
DNA-alkylating agents have a central role in the curative therapy of many human tumors; yet, resistance to these agents limits their effectiveness. The efficacy of the alkylating agent temozolomide has been attributed to the induction of O6-MeG, a DNA lesion repaired by the protein O6-methylguanine-DNA methyltransferase (MGMT). Resistance to temozolomide has been ascribed to elevated levels of ...
متن کاملRoles of base excision repair subpathways in correcting oxidized abasic sites in DNA.
Base excision DNA repair (BER) is fundamentally important in handling diverse lesions produced as a result of the intrinsic instability of DNA or by various endogenous and exogenous reactive species. Defects in the BER process have been associated with cancer susceptibility and neurodegenerative disorders. BER funnels diverse base lesions into a common intermediate, apurinic/apyrimidinic (AP) s...
متن کاملA method for detecting abasic sites in living cells: age-dependent changes in base excision repair.
Apurinic/apyrimidinic (AP) sites are common DNA lesions that arise from spontaneous depurination or by base excision repair (BER) of modified bases. A biotin-containing aldehyde-reactive probe (ARP) [Kubo, K., Ide, H., Wallace, S. S. & Kow, Y. W. (1992) Biochemistry 31, 3703-3708] is used to measure AP sites in living cells. ARP penetrates the plasma membrane of cells and reacts with AP sites i...
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ژورنال
عنوان ژورنال: Frontiers in Oncology
سال: 2012
ISSN: 2234-943X
DOI: 10.3389/fonc.2012.00176