EXCISION OF DNA-ADDUCTS OF NITROGEN MUSTARDS BY BACTERIAL AND MAMMALIAN 3-METHYLADENINE-DNA GLYCOSYLASES

Nitrogen mustards are among the DNA alkylating agents most widely used in chemotherapy. The homogeneous Escherichia coil AlkA protein (3-met hyladenine-DNA glycosylase II) is shown to excise damaged guanine and adenine bases from DNA modified by mechlorethamine, uracil mustard, ph enylalanine mustard and chlorambucil, and less efficiently acridine mu stard adducts, Homogeneous recombinant human and rat 3-methyladenine-D NA glycosylases excise adducts formed by nitrogen mustards less effici ently than the AlkA protein. In addition to the in vitro excision of a dducts, the AlkA protein eliminates cytotoxic mechlorethamine adducts from DNA in vivo.