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Role of DNA Repair in Resistance to Drugs that Alkylate O6 of Guanine

  • Omer N. Koç
  • Weldon P. PhillipsJr
  • Keunmyoung Lee
  • Lili Liu
  • Nasir H. Zaidi
  • James A. Allay
  • Stanton L. Gerson
Part of the Cancer Treatment and Research book series (CTAR, volume 87)

Abstract

This review focuses on DNA repair as a mechanism of resistance to chemotherapeutic agents that attack at the O6 position of guanine. This class of agents includes the methylating agents, temozolomide, procarbazine, dacarbazine (DTIC), and steptozotocin, and the chloroethylating agents, carmustine (1,3 bis-chloroethyl 2-nitrosourea, BCNU), lomustine (3-cyclohexyl-1-chloroethyl-nitrosourea, CCNU), (2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU), and agents used in other countries, including clomosome and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chlorethyl)-3-nitrosourea (ACNU). Both groups of agents attack at the same site, but their mechanism of cytotoxicity appears to differ. For instance, methylating agents form numerous methyl-DNA adducts, including O6-methylguanine (O6-mG). In cells with persistent O6-mG adducts, over 6,000 lesions are required to induce cell death [1]. In contrast, chloroethylating agents lead to the formation of DNA-interstrand crosslinks, only a few of which are required for cytotoxicity [2].

Keywords

Maximally Tolerate Dose Mismatch Repair MGMT Gene Peripheral Blood Mononuclear Methylating Agent 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Omer N. Koç
  • Weldon P. PhillipsJr
  • Keunmyoung Lee
  • Lili Liu
  • Nasir H. Zaidi
  • James A. Allay
  • Stanton L. Gerson

There are no affiliations available

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