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

Koç, Omer N.; Phillips, Weldon P.; Lee, Keunmyoung; Liu, Lili; Zaidi, Nasir H.; Allay, James A.; Gerson, Stanton L.

doi:10.1007/978-1-4613-1267-3_5

Omer N. Koç,
Weldon P. Phillips Jr,
Keunmyoung Lee,
Lili Liu,
Nasir H. Zaidi,
James A. Allay &
…
Stanton L. Gerson

Part of the book series: Cancer Treatment and Research ((CTAR,volume 87))

112 Accesses
12 Citations

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].

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Omer N. Koç
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Weldon P. Phillips Jr
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Keunmyoung Lee
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Lili Liu
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Nasir H. Zaidi
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James A. Allay
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Stanton L. Gerson
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The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA
William N. Hait M.D., Ph.D.
Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA
William N. Hait M.D., Ph.D.
Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 679 Hoes Lane, Room 242, Piscataway, NJ, 08854, USA
William N. Hait M.D., Ph.D.

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Koç, O.N. et al. (1996). Role of DNA Repair in Resistance to Drugs that Alkylate O⁶ of Guanine. In: Hait, W.N. (eds) Drug Resistance. Cancer Treatment and Research, vol 87. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1267-3_5

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DOI: https://doi.org/10.1007/978-1-4613-1267-3_5
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