Adducts of 6-Methylbenzo[a]pyrene and 6-Fluorobenzo[a]pyrene Formed by Electrochemical Oxidation in the Presence of Deoxyribonucleosides

N. V.S. RamaKrishna, Kai Ming Li, Eleanor G. Rogan, Ercole L. Cavalieri, Mathai George, Ronald L. Cerny, Michael L. Gross

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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-CH3BP) 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-(6-FBP-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-CH3BP in the presence of dG produced 8-(BP-6-CH2-yl)dG (5%) and a mixture of 7-(6-CH3BP-1-yl)Gua and 7-(6-CH3BP-3-yl)Gua (23%). The only adduct formed with dA was 3-(BP-6-CH2-yl)Ade (9%). 6-CH3BP did not afford any adducts with dC or dT. The noncarcinogenic 6-C1BP and 6-BrBP did not produce adducts with dG, dA, dC, or dT. These results are consistent with the chemical properties of the 6-FBP and 6-CH3BP radical cations; that is, 6-FBP reacts at C-1 and C-3, whereas 6-CH3BP reacts competitively at C-1 and C-3, as well as at the 6-CH3 position.

Original languageEnglish (US)
Pages (from-to)837-845
Number of pages9
JournalChemical Research in Toxicology
Volume6
Issue number6
DOIs
StatePublished - Nov 1 1993

ASJC Scopus subject areas

  • Toxicology

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