Role of DNA repair in resistance to drugs that alkylate O6 of guanine

Cancer Treat Res. 1996;87:123-46. doi: 10.1007/978-1-4613-1267-3_5.

Abstract

The mechanism of cytotoxicity of a number of chemotherapeutic agents involves alkylation at the O6 position of guanine, a site that strongly influences cytotoxicity. Repair of these lesions by the alkyltransferase protects from cytotoxicity and is a major mechanism of resistance to these agents. O6-benzylguanine inhibition of alkyltransferase sensitizes tumor cells, and clinical trials are underway to determine its efficacy. The use of gene therapy to enhance the expression of alkyltransferase in hematopoietic cells may prevent dose-limiting myelosuppression and may enhance the utility of this class of chemotherapeutic agents.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology*
  • DNA Repair*
  • Drug Resistance
  • Genetic Therapy
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • Humans
  • Methyltransferases / antagonists & inhibitors
  • Methyltransferases / chemistry
  • Methyltransferases / physiology*
  • Molecular Sequence Data
  • O(6)-Methylguanine-DNA Methyltransferase

Substances

  • Antineoplastic Agents, Alkylating
  • O(6)-benzylguanine
  • Guanine
  • Methyltransferases
  • O(6)-Methylguanine-DNA Methyltransferase