FORMATION OF THE CROSS-LINKED BASE, DIGUANYLETHANE, IN DNA TREATED WITH N,N'-BIS(2-CHLOROETHYL)-N-NITROSOUREA

Abstract

A cross-linked base, diguanylethane, was isolated and identified as a product of the reaction of [the antineoplastic drug] N,N''-bis(2-chloroethyl)-N-nitrosourea with [calf thymus] DNA. DNA was reacted at 37.degree. C with N,N''-bis(2-chloroethyl)-N-nitrosourea in neutral aqueous solution, isolated by precipitation with ethanol, washed and heated briefly at 100.degree. C to release a purine fraction. This fraction was separated by high-pressure liquid chromatography and contained chloroethylguanine and 1,2-diguanylethane. Formation of the latter product may be related to the cytotoxicity of N,N''-bis(2-chloroethyl)-N-nitrosourea.