DNA MODIFICATIONS DUE TO OXIDATIVE
DAMAGE
J. CADET 1 , M. BERGER, I. GIRAULT,
M.-F. INCARDONA, D. MOLKO, B. MORIN,
M. POLVERELLI, S. RAOUL and J.-L. RAVANAT
CEAlDepartement de Recherche Fondamentale sur la Matiere Condensee,
SCIBIlAN, F-38054 Grenoble Cedex 9, France
ABSTRACT
Modified purine and pyrimidine bases which constitute one of the major classes of
oxidative DNA damage are likely to be involved in mutagenesis and
carcinogenesis and possibly in aging. In the present survey, the currently
available information on the structural aspects of oxidized DNA bases and their
mechanism of formation are critically reviewed. A survey of the main approaches
(HPLC separations associated with various spectroscopic detections, gas
chromatography-mass spectrometry, postlabeling techniques, immunoassays ... )
involving either initial acid hydrolysis or enzymatic digestion of DNA which were
recently developed for monitoring the formation of oxidative DNA base damage in
cells, tissues and biological fluids is also presented. The measurement of the above
compounds in biological fluids such as urine may be used for assessing oxidative
damage to DNA [5]. Other important sources of oxidation processes are provided
by physical agents (ionizing radiation, near-ultraviolet/visible light [6,7]). In the
latter case, oxidation of DNA would require the presence of endogenous or
exogenous photosensitizers including flavins and porphyrins. In this short survey
emphasis has been placed on the oxidation reactions of the guanine moiety of
DNA and model compounds as the result of one-electron processes and exposure
to oxidizing agents including hydroxyl radicals and singlet oxygen. However, it
should be mentioned that relevant information on oxidation reactions of adenine,
cytosine and thymine, the other DNA bases is available [see for example, 6-10}.
Modifications de I'ADN par Oxydation
RESUME
L'oxydation des bases puriques et pyrimidiques, principaux composants de l'ADN
joue un role dans la mutagenese, la carcinogenese et peut-etre Ie vieillissement.
Dans ce travail, une revue des connaissances actuelles sur les aspects structuraux
des bases oxydees de l'ADN et sur les mecanismes de formation est discutee d'un
point de vue critique. Les principales approches analytiques sont presentees
(separation par CLHP associee a differentes detections spectroscopiques,
1 To whom correspondence may be addressed
C. Bardinet et al. (eds.), Geosciences and Water Resources: Environmental Data Modeling
© Springer-Verlag Berlin Heidelberg 1997
DAMAGE
J. CADET 1 , M. BERGER, I. GIRAULT,
M.-F. INCARDONA, D. MOLKO, B. MORIN,
M. POLVERELLI, S. RAOUL and J.-L. RAVANAT
CEAlDepartement de Recherche Fondamentale sur la Matiere Condensee,
SCIBIlAN, F-38054 Grenoble Cedex 9, France
ABSTRACT
Modified purine and pyrimidine bases which constitute one of the major classes of
oxidative DNA damage are likely to be involved in mutagenesis and
carcinogenesis and possibly in aging. In the present survey, the currently
available information on the structural aspects of oxidized DNA bases and their
mechanism of formation are critically reviewed. A survey of the main approaches
(HPLC separations associated with various spectroscopic detections, gas
chromatography-mass spectrometry, postlabeling techniques, immunoassays ... )
involving either initial acid hydrolysis or enzymatic digestion of DNA which were
recently developed for monitoring the formation of oxidative DNA base damage in
cells, tissues and biological fluids is also presented. The measurement of the above
compounds in biological fluids such as urine may be used for assessing oxidative
damage to DNA [5]. Other important sources of oxidation processes are provided
by physical agents (ionizing radiation, near-ultraviolet/visible light [6,7]). In the
latter case, oxidation of DNA would require the presence of endogenous or
exogenous photosensitizers including flavins and porphyrins. In this short survey
emphasis has been placed on the oxidation reactions of the guanine moiety of
DNA and model compounds as the result of one-electron processes and exposure
to oxidizing agents including hydroxyl radicals and singlet oxygen. However, it
should be mentioned that relevant information on oxidation reactions of adenine,
cytosine and thymine, the other DNA bases is available [see for example, 6-10}.
Modifications de I'ADN par Oxydation
RESUME
L'oxydation des bases puriques et pyrimidiques, principaux composants de l'ADN
joue un role dans la mutagenese, la carcinogenese et peut-etre Ie vieillissement.
Dans ce travail, une revue des connaissances actuelles sur les aspects structuraux
des bases oxydees de l'ADN et sur les mecanismes de formation est discutee d'un
point de vue critique. Les principales approches analytiques sont presentees
(separation par CLHP associee a differentes detections spectroscopiques,
1 To whom correspondence may be addressed
C. Bardinet et al. (eds.), Geosciences and Water Resources: Environmental Data Modeling
© Springer-Verlag Berlin Heidelberg 1997