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 coli AlkA protein (3-methyladenine-DNA glycosylase II) is shown to excise damaged guanine and adenine bases from DNA modified by mechlorethamine, uracil mustard, phenylalanine mustard and chlorambucil, and less efficiently acridine mustard adducts. Homogeneous recombinant human and rat 3-methyladenine-DNA glycosylases excise adducts formed by nitrogen mustards less efficiently than the AlkA protein. In addition to the in vitro excision of adducts, the AlkA protein eliminates cytotoxic mechlorethamine adducts from DNA in vivo.
Mattes
W B
WB
Groupe Réparation des lesions radio- et chimioinduites, CNRS URA147, Institut Gustave-Roussy, Villejuif, France.
Lee
C S
CS
Laval
J
J
O'Connor
T R
TR
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001483:Base Sequence; D002699:Chlorambucil / Q000494:pharmacology; D018736:DNA Adducts; D045647:DNA Glycosylases; D004926:Escherichia coli / Q000201:enzymology*; D006147:Guanine / Q000378:metabolism; D006801:Humans; D008466:Mechlorethamine / Q000494:pharmacology*; D008558:Melphalan / Q000494:pharmacology; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D051381:Rats
D018906:Antineoplastic Agents, Alkylating; D018736:DNA Adducts; D002699:Chlorambucil; D008466:Mechlorethamine; D006147:Guanine; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D008558:Melphalan