Formation of DNA Interstrand Cross-Links by the Novel Chloroethylating Agent 2-Chloroethyl(methylsulfonyl)methanesulfonate: Suppression by O6-Alkylguanine-DNA Alkyltransferase Purified from Human Leukemic Lvmnhoblasts

Thomas P. Brent*, Steven O. Lestrud, Debra G. Smith, Joanna S. Remack

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The formation of DNA interstrand cross-links was compared in DNA treated with either 13-bis(2-chloroethyl)-l-nitrosourea or 2-chloroethyl-(methylsulfonyl)methanesulfonate. DNA that was pulse treated briefly with either of these drugs continued to form cross-links at 37°C for over 8 h after drug removal, indicating that such DNA contained stable precursors of cross-links. When human O6-alkylguanine-DNA alkyltransferase was added to the drug-treated DNA further cross-link formation was prevented at all points during this protracted time course, indicating that these stable cross-link precursors also remained substrates for this repair enzyme. Although the pattern of 2-chloroethyl(methylsulfonyl)methanesulfonate-induced cross-link formation and susceptibility to suppression by O6-alkylguanine-DNA alkyltransferase resembled that for 1, 3-bis(2-chloroethyL)-1-nitrosourea, quantitative differences in the rates of cross-link formation and in the amounts of O6 alky guanine-DNA alkyltransferase required to suppress cross-link formation suggest that critical differences exist between these agents.

Original languageEnglish (US)
Pages (from-to)3384-3387
Number of pages4
JournalCancer Research
Volume47
Issue number13
StatePublished - Jul 1987

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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