Mechanism of glutathione-mediated DNA damage by the antineoplastic agent 1,3-bis(2-chloroethyl)-N-nitrosourea.

S-[(2-Chloroethyl)carbamoyl]glutathione (SCCG), a compound formed during the decomposition of BCNU in the presence of GSH, induces DNA damage in a human lymphoblastoid cell line. This GSH conjugate was shown by direct fast atom bombardment mass spectrometric analysis to transfer an aminoethyl group to the N-7 position of guanosine. The resulting N7-(aminoethyl)guanosine adduct readily undergoes depurination. From these model studies, DNA aminoethylation appears to represent a plausible explanation as the major cause for the DNA-damaging effects exerted by SCCG.