282
Ecotoxicological Issues
chromatographie gaze use - spectrometrie de masse, technique de post marquage,
immunologie, ... } avec soit une hydrolyse acide initiale, soit une digestion
enzymatique de I'ADN. Ces pretraitements ont ete recemment developpes pour
suivre l'oxydation de l'ADN dans les cellules, les tissus, et les liquides biologiques.
L'analyse de ces composes dans les milieux biologiques tels que l'urine, peut erre
utilisee pour estimer les deguts de l'oxydation sur I'ADN [5]. Le processus oxydatif
de I'ADN peut erre egalement etudie au moyen d'agents physiques (radiations
ionisantes, lumiere dans l'ultra violet proche/visible [6,7]). Dans ce dernier cas, la
reaction d'oxydation de l'ADN necessitera la presence d'agents de photosensibilisation endogenes ou exogenes dont les flavines et les porphyrines. Ce court expose
s'interesse principalement aux reactions d'oxydation de la guanine de l'ADN et de
composes modeles telles que celles resultant de processus a un electron et de
l'exposition a des agents oxydants (radicaux hydroxyles et oxygene singulet). Des
informations pertinentes sur les reactions d'oxydation de l'adenine, la cytosine et
la thymine, autres constituants de l'ADN, peuvent etre egalement trouvees dans la
litterature [voir 6-10].
1 RESULTS AND DISCUSSION
The main reactive oxygen species are listed in Table 1. Their reactivity towards
DNA components and the chemical reactions of base radical cations that are
produced by one-electron reactions are also mentioned. It clearly appears that OH
radical and related reactive species including ferry I ions, both of them possibly
generated through the Haber-Weiss reaction within cells, are the most reactive
agents. Base lesions, abasic sites, DNA strand breaks and DNA-protein crosslinks
represent the four main classes of oxidized base damage. The complex nature of
the oxidation reactions of the base moieties of DNA is illustrated by considering
guanine, the nucleobase which presents the lowest ionization potential among
DNA components.
1 .1 Oxidation reactions of the DNA guanine moiety
1.1.1 Radical processes involving OH radical and one-electron
oxidation
The two overwhelming oxidation products of the purine moiety of
2'-deoxyguanosine (1) as resulting from both the reaction OH. radical and the
transformation of the guanine radical cation (one-electron oxidation) have been
isolated and identified as :
2,2-diamino-4-[(2-deoxy-B-D-erythro-pentofuranosyl)amino]-5(2H)-oxazolone
(6)
and its precursor [10,11] :
2-amino-5-[(2-deoxy-B-D-erythro-pentofuranosyl)amino]-4H-imidazol-4-one
(5)
The mechanism of their production as depicted in Figure 1 may be rationalized in
terms of transient formation of the oxidizing guanilyl radical 3 which may arise
either from dehydration of the OH. adduct at C-4 4 or deprotonation of the
guanine radical cation 2.
Ecotoxicological Issues
chromatographie gaze use - spectrometrie de masse, technique de post marquage,
immunologie, ... } avec soit une hydrolyse acide initiale, soit une digestion
enzymatique de I'ADN. Ces pretraitements ont ete recemment developpes pour
suivre l'oxydation de l'ADN dans les cellules, les tissus, et les liquides biologiques.
L'analyse de ces composes dans les milieux biologiques tels que l'urine, peut erre
utilisee pour estimer les deguts de l'oxydation sur I'ADN [5]. Le processus oxydatif
de I'ADN peut erre egalement etudie au moyen d'agents physiques (radiations
ionisantes, lumiere dans l'ultra violet proche/visible [6,7]). Dans ce dernier cas, la
reaction d'oxydation de l'ADN necessitera la presence d'agents de photosensibilisation endogenes ou exogenes dont les flavines et les porphyrines. Ce court expose
s'interesse principalement aux reactions d'oxydation de la guanine de l'ADN et de
composes modeles telles que celles resultant de processus a un electron et de
l'exposition a des agents oxydants (radicaux hydroxyles et oxygene singulet). Des
informations pertinentes sur les reactions d'oxydation de l'adenine, la cytosine et
la thymine, autres constituants de l'ADN, peuvent etre egalement trouvees dans la
litterature [voir 6-10].
1 RESULTS AND DISCUSSION
The main reactive oxygen species are listed in Table 1. Their reactivity towards
DNA components and the chemical reactions of base radical cations that are
produced by one-electron reactions are also mentioned. It clearly appears that OH
radical and related reactive species including ferry I ions, both of them possibly
generated through the Haber-Weiss reaction within cells, are the most reactive
agents. Base lesions, abasic sites, DNA strand breaks and DNA-protein crosslinks
represent the four main classes of oxidized base damage. The complex nature of
the oxidation reactions of the base moieties of DNA is illustrated by considering
guanine, the nucleobase which presents the lowest ionization potential among
DNA components.
1 .1 Oxidation reactions of the DNA guanine moiety
1.1.1 Radical processes involving OH radical and one-electron
oxidation
The two overwhelming oxidation products of the purine moiety of
2'-deoxyguanosine (1) as resulting from both the reaction OH. radical and the
transformation of the guanine radical cation (one-electron oxidation) have been
isolated and identified as :
2,2-diamino-4-[(2-deoxy-B-D-erythro-pentofuranosyl)amino]-5(2H)-oxazolone
(6)
and its precursor [10,11] :
2-amino-5-[(2-deoxy-B-D-erythro-pentofuranosyl)amino]-4H-imidazol-4-one
(5)
The mechanism of their production as depicted in Figure 1 may be rationalized in
terms of transient formation of the oxidizing guanilyl radical 3 which may arise
either from dehydration of the OH. adduct at C-4 4 or deprotonation of the
guanine radical cation 2.