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Adducts of 6-methylbenzo[a]pyrene and 6-fluorobenzo[a]pyrene formed by electrochemical oxidation in the presence of deoxyribonucleosides

Journal Article · · Chemical Research in Toxicology; (United States)
DOI:https://doi.org/10.1021/tx00036a013· OSTI ID:6955813
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  1. Univ. of Nebraska Medical Center, Omaha, NE (United States)

Studies of the DNA adducts of benzo[a]pyrene and selected derivatives are part of the strategy to elucidate mechanisms of tumor initiation by aromatic hydrocarbons. Reference adducts formed by reaction of deoxyribonucleosides with electrophilic intermediates of 6-fluorobenzo[a]pyrene (6-FBP) and 6-methylbenzo[a]pyrene (6-CH[sub 3]BP) are investigated here because they are essential for identifying the structures of adducts formed in biological systems. Electrochemical oxidation of 6-FBP in the presence of deoxyribonucleosides led to adducts from the 6-FBP radical cation. With dG, a mixture of 6-FBP bound at C-1 or C-3 to the N-7 of Gua was formed in 10% yield, whereas 6-FBP plus dC gave a mixture of 3-(6FBP-1-yl)Cyt and 3-(6-FBP-3-yl)Cyt (15%). No adducts of 6-FBP were formed with dA or dT. Electrochemical oxidation of 6-CH[sub 3]BP in the presence of dG produced 8-(BP-6CH[sub 2]-yl)dG (5%) and a mixture of 7-(6-CH[sub 3]BP-1-yl)Gua and 7-(6-CH[sub 3]BP-3-yl)Gua (23%). The only adduct formed with dA was 3-(BP-6-CH[sub 2]-yl)Ade (9%). 6-CH[sub 3]Bp did not afford any adducts with dC or dT. The noncarcinogenic 6-ClBP and 6-BrBP did not afford any adducts with dG, dA, dC, or dT. These results are consistent with the chemical properties of the 6-FBP and 6-CH[sub 3]BP radical cations; that is, 6-FBP reacts at C-1 and C-3, whereas 6-CH[sub 3]BP reacts competitively at C-1 and C-3, as well as the 6-CH[sub 3] position. 18 refs., 7 figs., 1 tab.

OSTI ID:
6955813
Journal Information:
Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 6:6; ISSN CRTOEC; ISSN 0893-228X
Country of Publication:
United States
Language:
English