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.
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 degrees 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-alkylguanine-DNA alkyltransferase required to suppress cross-link formation suggest that critical differences exist between these agents.
D002330:Carmustine / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000201:enzymology*; D008214:Lymphocytes / Q000201:enzymology; D008698:Mesylates / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism*; D019853:O(6)-Methylguanine-DNA Methyltransferase
D003432:Cross-Linking Reagents; D008698:Mesylates; C041189:clomesone; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002330:Carmustine