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.
Stahl
W
W
Fachbereich Chemie, Universitaet Kaiserslautern, Germany.
Lenhardt
S
S
Przybylski
M
M
Eisenbrand
G
G
D002330:Carmustine / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D005978:Glutathione / Q000031:analogs & derivatives / Q000737:chemistry / Q000502:physiology* / Q000633:toxicity; D006151:Guanosine / Q000737:chemistry; D006801:Humans; D009153:Mutagens / Q000633:toxicity; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D009153:Mutagens; D006151:Guanosine; C074485:S-((2-chloroethyl)carbamoyl)glutathione; D005978:Glutathione; D002330:Carmustine