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 Cavalieri, Eleanor G Rogan

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 - Oct 29 1996

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Liver
Rats
Liver Microsomes
DNA
Deoxyribose
Aromatic Hydrocarbons
Skin
DNA Cleavage
Methylcholanthrene
DNA Adducts
Benzo(a)pyrene
Polycyclic Aromatic Hydrocarbons
Epoxy Compounds
NADP
Wistar Rats
Fluorescence
Electrons
Temperature
Chemical activation
Oxidation

ASJC Scopus subject areas

  • Toxicology

Cite this

Devanesan, P. D., Higginbotham, S., Ariese, F., Jankowiak, R., Suh, M., Small, G. J., ... Rogan, E. G. (1996). Depurinating and stable benzo[a]pyrene-DNA adducts formed in isolated rat liver nuclei. Chemical Research in Toxicology, 9(7), 1113-1116. https://doi.org/10.1021/tx9600513

Depurinating and stable benzo[a]pyrene-DNA adducts formed in isolated rat liver nuclei. / Devanesan, Prabhakar D.; Higginbotham, Sheila; Ariese, Freek; Jankowiak, Ryszard; Suh, Myungkoo; Small, Gerald J.; Cavalieri, Ercole; Rogan, Eleanor G.

In: Chemical Research in Toxicology, Vol. 9, No. 7, 29.10.1996, p. 1113-1116.

Research output: Contribution to journalArticle

Devanesan PD, Higginbotham S, Ariese F, Jankowiak R, Suh M, Small GJ et al. Depurinating and stable benzo[a]pyrene-DNA adducts formed in isolated rat liver nuclei. Chemical Research in Toxicology. 1996 Oct 29;9(7):1113-1116. https://doi.org/10.1021/tx9600513
Devanesan, Prabhakar D. ; Higginbotham, Sheila ; Ariese, Freek ; Jankowiak, Ryszard ; Suh, Myungkoo ; Small, Gerald J. ; Cavalieri, Ercole ; Rogan, Eleanor G. / Depurinating and stable benzo[a]pyrene-DNA adducts formed in isolated rat liver nuclei. In: Chemical Research in Toxicology. 1996 ; Vol. 9, No. 7. pp. 1113-1116.
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