Reaction of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) with guanosine: evidence for a new mechanism of DNA modification.
When guanosine reacts with 1,3-bis(2-chloro-2,2-dideuteroethyl)-1-nitrosourea in a mixture of pH 7.1 buffer and DMSO, the 7-chloroethylguanosine which is isolated contains two deuterium atoms located next to the guanine ring and beta to the chlorine atom as shown by electron impact mass spectrometry. It is proposed that initial attack by DNA bases occurs on the number 2 carbon of the haloethylnitrosourea with displacement of the chloride ion. In accordance with this proposed mechanism, 7-bromoethylguanosine is isolated as a major product when BCNU is reacted with guanosine in the presence of high concentrations of KBr. These results suggest that the antitumor activity of various haloethylating antitumor agents may be determined by structural changes which affect their mechanisms of reaction with DNA.
D002330:Carmustine / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D006151:Guanosine
D006151:Guanosine; D004247:DNA; D003903:Deuterium; D002330:Carmustine