Identification of adducts formed in reactions of 2 '-deoxyadenosine and calf thymus DNA with the bacterial mutagen 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone
T. Munter et al., Identification of adducts formed in reactions of 2 '-deoxyadenosine and calf thymus DNA with the bacterial mutagen 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone, CHEM RES T, 12(12), 1999, pp. 1205-1212
3-Chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF) is a strong direc
t acting bacterial mutagen found in chlorine-disinfected drinking water. We
studied the reaction of CMCF with 2'-deoxyadenosine;in buffered aqueous so
lutions and found that three main adducts were formed. The adducts were iso
lated and purified by C18 column chromatography and HPLC, and characterized
on the basis of their UV absorbance, fluorescence emission, H-1 and C-13 N
MR spectroscopic, and mass spectrometric features. The adducts were identif
ied as 3-(2'-deoxy-beta-D-ribofuranosyl) -7H-8-formyl[2, 1-i]pyrimidopurine
(pfA-dR), 3-(2'-deoxy-beta-D-ribofuranosyl)-7H-8-carboxy[2,1-i]pyrimidopur
ine (pcA-dR), and 4-(N-6-2'-deoxyadenosinyl)-3-formyl-2-hydroxy-3-butenoic
acid (OH-fbaA-dR). In the reactions performed at pH 7.4 and 37 degrees C, t
he yields of pfA-dR, pcA-dR, and OH-fbaA-dR were 1.1, 6.7, and 5.5 mol %, r
espectively. The adduct pfA-dR was detected also in calf thymus DNA reacted
with CMCF. The yield was about six adducts per 10(5) bases. To elucidate t
he mechanisms of formation of the adducts, C-13-3-labeled CMCF was reacted
with 2'-deoxyadenosine. The adducts are structurally related to the adducts
previously identified in the reactions of structurally analogous chlorohyd
roxyfuranones with 2'-deoxyadenosine.