Type I and Type II Photosensitized Oxidative Modification of
2‘-Deoxyguanosine (dGuo) by Triplet-Excited Ketones
Generated Thermally from the 1,2-Dioxetane HTMD
posted on 1997-01-29, 00:00authored byWaldemar Adam, Chantu R. Saha-Möller, André Schönberger
The nucleoside 2‘-deoxyguanosine (dGuo) was treated with
3-(hydroxymethyl)-3,4,4-trimethyl-1,2-dioxetane
(HTMD), the latter generates efficiently triplet-excited carbonyl
products on thermal decomposition in the dark.
The type I photooxidation products,
2,2-diamino-[(2-deoxy-β-d-erythro-pentofuranosyl)-4-amino]-5(2H)-oxazolone
(oxazolone) and the cyclic nucleoside
2-(S)-2,5‘-anhydro-1-(2-deoxy-β-d-erythro-pentofuranosyl)-5-guanidinylidene-2-hydroxy-4-oxoimidazolidine (oxoimidazolidine), as well as the type II
photooxidation products 4-(R)*- and
4-(S)*-4-hydroxy-8-oxo-4,8-dihydro-2‘-deoxyguanosine (4-HO-8-oxodGuo) and
8-oxo-7,8-dihydro-2‘-deoxyguanosine (8-oxodGuo), were quantitatively determined by appropriate selective and
sensitive HPLC assays. The concentration
and time profiles revealed that about 40% of the triplet ketones
derived from the thermal decomposition of HTMD
led to photooxidation of dGuo. Essentially equal amounts of type I
and type II photooxidation products were found,
as could be established by comparison with predominant type I
(benzophenone, riboflavin) and type II (Rose Bengal,
methylene blue) photosensitizers. The participation of singlet
oxygen (type II activity) was confirmed by the substantial
D2O effect in the formation of 8-oxodGuo. The results
demonstrate that dioxetanes, particularly HTMD, are
efficient
photooxidants of dGuo on thermal activation in the dark and
constitute excellent chemical tools to study
photobiological processes without the use of light, in the
present case, photogenotoxicity.