Characterization of adducts formed in the reaction of glutaraldehyde with 2'-deoxyadenosine.
Glutaraldehyde (1,5-pentanedial) is a widely used industrial chemical that has been found to be mutagenic in bacteria and mammalian cells. In this study, we examined the reaction of glutaraldehyde with 2'-deoxyadenosine and calf thymus DNA in aqueous buffered solutions. The 2'-deoxyadenosine adducts were isolated by reversed phase HPLC and characterized by their UV absorbance and 1H and 13C NMR spectroscopic and mass spectrometric features. The reaction produced three major adducts. The adduct dA567 was derived from two 2'-deoxyadenosine units bound together with a piperidine unit, and its yield was 10.4%. The carbons of the piperidine ring originated from glutaraldehyde, whereas the nitrogen of the ring originated from the exocyclic amino group of one of the 2'-deoxyadenosine units. The adduct dA451d (yield 0.6%) was similar in structure to dA567, but one of the deoxyribose moieties from 2'-deoxyadenosine was missing. The third adduct, dA334, consisted of a hydroxy-tetrahydropyridine moiety derived from glutaraldehyde and N6 of 2'-deoxyadenosine (yield 4.0%). Furthermore, LC-ESI-MS/MS analysis of the reaction mixture revealed the formation of compounds with ion peaks of m/z = 352. None of these compounds were sufficiently stable for preparative isolation. They were tentatively identified as a pair of diastereomers of 2,6-dihydroxypiperidine derivatives, which are likely precursors to dA334. Plausible mechanisms for the formation of the adducts are presented. In the reaction of glutaraldehyde with single and double stranded calf thymus DNA, the dA334 adduct was formed.
Olsen
Raymond
R
National Institute of Occupational Health, P.O. Box 8149 Dep., N-0033 Oslo, Norway.
Backman
Josefin
J
Molander
Paal
P
Øvrebø
Steinar
S
Thorud
Syvert
S
Lundanes
Elsa
E
Greibrokk
Tyge
T
Kronberg
Leif
L
D000818:Animals; D002247:Carbon Isotopes; D002384:Catalysis; D002853:Chromatography, Liquid; D004247:DNA / Q000737:chemistry* / Q000302:isolation & purification; D018736:DNA Adducts / Q000032:analysis / Q000737:chemistry*; D003839:Deoxyadenosines / Q000737:chemistry*; D003853:Deoxyribonucleosides / Q000737:chemistry; D003855:Deoxyribose / Q000737:chemistry; D005976:Glutaral / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D019906:Nuclear Magnetic Resonance, Biomolecular; D011684:Purine Nucleosides / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry
D002247:Carbon Isotopes; D018736:DNA Adducts; D003839:Deoxyadenosines; D003853:Deoxyribonucleosides; D011684:Purine Nucleosides; D003855:Deoxyribose; D004247:DNA; C427203:calf thymus DNA; C058118:2'-deoxyadenosine; D005976:Glutaral