Depurinating and stable benzo[a]pyrene-DNA adducts formed in isolated rat liver nuclei

Prabhakar D. Devanesan, Sheila Higginbotham, Freek Ariese, Ryszard Jankowiak, Myungkoo Suh, Gerald J. Small, Ercole L. Cavalieri, Eleanor G. Rogan

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Polycyclic aromatic hydrocarbons are bound to DNA by two major pathways, one-electron oxidation and monooxygenation, to form adducts that are stable in DNA under normal conditions of isolation and depurinating adducts that are released from DNA by cleavage of the bond between the purine base and deoxyribose. Isolated rat liver nuclei have been used as an in vitro model for studying covalent binding of aromatic hydrocarbons to DNA, but the depurinating adducts formed by nuclei have not been identified or compared to those formed by the more commonly used rat liver microsomes. To examine the profiles of stable and depurinating adducts, nuclei from the livers of 3- methylcholanthrene-induced male MRC Wistar rats were incubated with [3H]benzo[a]pyrene (BP) and NADPH. Three depurinating adducts, 8-(BP-6- yl)Gua, 7-(BP-6-yl)Gua, and 7-(BP-6-yl)Ade, were obtained from the nuclei, as seen previously with rat liver microsomes or in mouse skin. The profile of stable adducts analyzed by the 32P-postlabeling method was qualitatively similar to that found in the microsomal activation of BP or in mouse skin treated with BP. Low-temperature fluorescence studies of the nuclear DNA revealed the presence of stable BP adducts originating from syn- and anti-BP diol epoxide.

Original languageEnglish (US)
Pages (from-to)1113-1116
Number of pages4
JournalChemical Research in Toxicology
Volume9
Issue number7
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Depurinating and stable benzo[a]pyrene-DNA adducts formed in isolated rat liver nuclei'. Together they form a unique fingerprint.

  • Cite this