MOLECULAR DOSIMETRY OF DNA ADDUCTS IN C3H MICE TREATED WITH GLYCIDALDEHYDE

The formation of DNA adducts in he skin of male C3H mice treated cutaneously with glycidaldehyde (2 or 10 mg/animal) in acetone has been investigated by HPLC coupled with fluorescence detection and P-32-postlabelling analysis. Following a 24 h exposure period, epidermal DNA was isolated from treated dorsal skin and enzymically digested to nucleoside-3'-monophosphates. HPLC-P-32-postlabelling analysis of the DNA hydrolysate indicated that a single major cyclic adduct was formed from the reaction of glycidaldehyde with deoxyadenosine residues in mouse skin DNA. This adduct was identified as 3-beta-D-deoxyribofuranosyl-7-(hydroxymethyl)-3H-imidazo [2,1-i]purine-3'-monophosphate by comparison with a synthetic standard. This adduct was stable, strongly fluorescent and readily detected by HPLC with fluorescence detection. There was no evidence for the formation of deoxyguanosine adducts in epidermal DNA of treated animals. Glycidaldehyde also reacted with calf thymus DNA in vitro at pH 7.0 to give the same deoxyadenosine adduct observed in vivo. At pH 10, however, this was a relatively minor product and the major adduct was 5,9-dihydro-7-[hydroxymethyl)-9-oxo-3-beta-D-deoxyribofuranosyl-3H-imidazo [1,2-a]purine-3'-monophosphate formed by the initial reaction of glycidaldehyde with deoxyguanosine residues.