Reaction of epichlorohydrin with adenosine, 2′-deoxyadenosine and calf thymus DNA: Identification of adducts

Epichlorohydrin (a probable human carcinogen) was allowed to react with adenosine and the adducts were characterized by NMR and UV spectroscopy, and mass spectrometry. The adduct initially formed was 1-(3-chloro-2-hydroxypropyl)-adenosine, which subsequently ring closures to 1,N6-(2-hydroxypropyl)-adenosine at neutral and basic conditions. At acid conditions, the N-1 adduct undergoes a slow deamination to yield 1-(3-chloro-2-hydroxypropyl)-inosine. Minor adducts identified were 7-(3-chloro-2-hydroxypropyl)-adenosine and 3-(3-chloro-2-hydroxypropyl)-adenosine which are easily deglycosylated, and an adduct where the epichlorohydrin residue was attached to the sugar moiety of adenosine. A diadduct, 1,N6-(2-hydroxypropyl)-N6-(3-chloro-2-hydroxypropyl)-adenosine was also identified. The reaction of epichlorohydrin with calf thymus DNA gave 1,N6-(2-hydroxypropyl)-deoxyadenosine and 3-(3-chloro-2-hydroxypropyl)-adenine (major adduct).