Crosslinking of DNA by busulfan. Formation of diguanyl derivatives

Abstract

High-pressure liquid chromatography has been used to separate the derivatives of guanosine which are formed when this nucleoside is reacted with busulfan. Derivatives which have been identified by a combination of ultraviolet and mass spectrometry include: 7-(delta-hydroxybutyl)guanosine, 1,4-di(7-guanosyl)butane, and 1-(7-guanyl)-4-(7-guanosinyl)butane. The latter two derivatives can be converted to 1,4-di(7-guanyl)butane by mild acid hydrolysis. Using 1,4-di(7-guanyl)butane as a marker for high-pressure liquid chromatography, we have identified this compound as a product of the reaction between DNA and busulfan. These findings verify the previously unconfirmed report that busulfan is a crosslinking agent for DNA and strengthen the hypothesis that differences in the biological properties of alkylating agents result from differences in their reactions with DNA.