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

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.