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.
3-Chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF) is a strong direct acting bacterial mutagen found in chlorine-disinfected drinking water. We studied the reaction of CMCF with 2-deoxyadenosine in buffered aqueous solutions and found that three main adducts were formed. The adducts were isolated and purified by C18 column chromatography and HPLC, and characterized on the basis of their UV absorbance, fluorescence emission, (1)H and (13)C NMR spectroscopic, and mass spectrometric features. The adducts were identified 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]pyrimidopurine++ + (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, the yields of pfA-dR, pcA-dR, and OH-fbaA-dR were 1.1, 6.7, and 5.5 mol %, respectively. 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 the mechanisms of formation of the adducts, (13)C-3-labeled CMCF was reacted with 2'-deoxyadenosine. The adducts are structurally related to the adducts previously identified in the reactions of structurally analogous chlorohydroxyfuranones with 2-deoxyadenosine.
Munter
T
T
Department of Organic Chemistry, Abo Akademi University, Biskopsgatan 8, FIN-20500 Turku/Abo, Finland.
Le Curieux
F
F
Sjöholm
R
R
Kronberg
L
L
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts / Q000032:analysis*; D004249:DNA Damage; D003839:Deoxyadenosines / Q000737:chemistry*; D005663:Furans / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009153:Mutagens / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
D018736:DNA Adducts; D003839:Deoxyadenosines; D005663:Furans; D009153:Mutagens; C092013:3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone; D004247:DNA