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 LYMPHOBLASTS

  • 1 July 1987
    • journal article
    • research article
    • Vol. 47  (13) , 3384-3387
Abstract
The formation of DNA interstrand cross-links was compared in DNA treated with either 1,3-bis(2-chloroethyl)-1-nitrosourea or 2-chloroethyl(methylsulfonyl)methanesulfonate. DNA that was pulse treated briefly with either of these drugs continued to form cross-links at 37.degree. C for over 8 h after drug removal, indicating that such DNA contained stable precursors of cross-links. When human 06-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 06-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 06-alkylguanine-DNA alkyltransferase required to suppress cross-link formation suggest that critical differences exist between these agents.