Secondary oxidation of cyclic 1,N2-propano and 1,N2-etheno-2'-deoxyguanosine DNA adducts. Consequences in oxidative stress biomarker development.
This work is an attempt to investigate the chemical stability of 1,N2-propano-2'-deoxyguanosine (pdG-HNE) and 1,N2-etheno-2'-deoxyguanosine (epsilondG) DNA adducts against hydrolysis and upon oxidation reactions. It includes both kinetic issues together with proposed degradation pathways. While both chemicals are stable in the 3.5-9 pH range, the results suggest that pdG-HNE adduct is less prone to in vitro oxidative transformation than epsilondG adduct. EpsilondG and pdG-HNE behave differently upon hydroxyl radical and one electron oxidation reactions. The exocyclic ring of epsilondG is mainly affected by oxidative processes leading to the regeneration of 2'-deoxyguanosine (dG) while the integrity of the exocyclic ring is preserved for pdG-HNE. Consequently, pdG-HNE might be a better biomarker than epsilondG for monitoring oxidative stress during environmental or occupational exposures to chemicals. Understanding the in vitro routes of etheno and propano DNA adduct degradation would probably help to guide the development of analytical methodologies for the reliable detection of these endogenous adducts.
Barbati
Stéphane
S
Laboratoire Chimie Provence, Aix-Marseille Universités-CNRS (UMR 6264), 3 Place Victor Hugo, 13331 Marseille Cedex 3, France.
Bonnefoy
Aurélie
A
Botta
Alain
A
Chiron
Serge
S
D015415:Biomarkers / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000737:chemistry*; D003839:Deoxyadenosines / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004784:Environmental Monitoring; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000737:chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D016273:Occupational Exposure; D010084:Oxidation-Reduction; D018384:Oxidative Stress
C553598:1,N2-propano-2'-deoxyguanosine; D015415:Biomarkers; D018736:DNA Adducts; D003839:Deoxyadenosines; D017665:Hydroxyl Radical; C032221:1,N(6)-ethenodeoxyadenosine; D003849:Deoxyguanosine