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© 1992 Oxford University Press

research-article

Molecular dosimetry of DNA adducts in C3H mice treated with bisphenol A diglycidylether

Sandra Steiner 1, Gideon Hönger and Peter Sagelsdorff 2

Ciba-Geigy Ltd. Toxicology Services, Cell Biology Basel, CH-4002, Switzerland
1Present address: Sandoz Ltd. Toxicology CH-4132 Muttenz, Switzerland

2To whom correspondence should be addressed

The formation of a glycidaldehyde — DNA adduct In skin of C3H mice treated with [14C]bisphenol A diglycidylether has been previously reported and it was assumed that the modification occurred on guanine residues. We were interested in elucidating the structure of this glycidaldehyde-DNA adduct by using a non-radioactive approach. Male C3H mice were treated with a single topical dose of 2 mg bisphenol A diglycidylether in acetone for 48, 96 or 192 h. An additional two mice were treated with 2 mg glycidaldehyde in acetone for 24 h. Epidermal DNA was isolated and enzymatlcally digested to nucleoside-3'-monophosphates. Aliquots of the DNA hydrolysates were separated on HPLC using a reversephase column with a potassium dihydrogen phosphate/methanol gradient. Fluorescence analysis of the eluent indicated the presence of a fluorescent DNA adduct, which was identified as hydroxymethylethenodeoxyadenosine-3'- monophosphate by comparison with a synthetic reference standard. Amounts of adducts were detennined by fluorescence measurements using a calibration curve obtained with the authentic adduct standard. Irrespective of duration of exposure, all DNA hydrolysates of treated mice contained similar amounts of the deoxyadenosine adduct. The alkylation frequency was 0.1–0.8 and 166 adducts/106 normal nucleotides for the treatment with bisphenol A diglycidylether and glycidaldehyde respectively. The limit of detection using 500 µg DNA samples for analysis was ~0.03 adducts/l06 normal nucleotides.


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