Reaction of DNA with glycidaldehyde. Isolation and identification of a deoxyguanosine reaction product

Abstract

Glycidaldehyde, a bifunctional carcinogenic alkylating agent, has been found to react with calf thymus DNA in vitro under alkaline conditions. A product was isolated and identified to be the result of a fusion of a delta4-imidazoline ring to the pyrimidine ring of deoxyguanosine at the N-1 and 2-NH2 positions. Following reaction and dialysis, the DNA was hydrolyzed enzymatically to nucleosides. The structural assignment of the product was based on comparison of the elution volume from a Sephadex G-10 column, the ultraviolet spectra at various conditions of pH, and the thin layer chromatographic properties with respect to an authentic sample. The formation of the extended ring system with DNA-derived guanosine may be related to the mode of carcinogenic action of this difunctional alkylating agent.