Identification and quantitation of benzo[a]pyrene-DNA adducts formed in mouse skin

Journal Article · · Chemical Research in Toxicology; (United States)

DOI:https://doi.org/10.1021/tx00033a017· OSTI ID:7026084

Rogan, E G; Devanesan, D; RamaKrishna, N V.S.; Higginbotham, S; Padmavathi, N S; Chapman, K; Cavalieri, E L ^[1]; Jeong, H; Jankowiak, R; Small, G J ^[2]

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1. Univ. of Nebraska Medical Center, Omaha, NE (United States)
2. Iowa State Univ., Ames, IA (United States)

The DNA adducts of benzo[a]pyrene (BP) formed in vitro were previously identified and quantitated. In this paper, we report the identification and quantitation of the depurination adducts of BP, 8-(benzo[a]pyrene-6-yl)guanine (BP-6-C8Gua), BP-6-N7Gua, and BP-6-N7Ade, formed in mouse skin by one-electron oxidation, as well as the major stable adduct formed via the diolepoxide pathway, BP diolepoxide bound at C-10 to the 2-amino of dG (BPDE-10-N[sup 2]dG). Identification of the depurination adducts was achieved by HPLC and fluorescence line narrowing spectroscopy. The depurination adducts, BP-6-C8Gua (34%), BP-6-N7Gua (10%), and BP-6-N7Ade (30%), constituted 74% of the adducts found in mouse skin 4 h after treatment with BP. The stable adduct BPDE-10-N[sup 2]dG accounted for 22% of the adducts. Treatment of the skin with BP-7,8-dihydrodiol or BP diolepoxide yielded almost exclusively the stable adduct BPDE-10-N[sup 2]dG. When BP or BP-7,8-dihydrodiol was bound to RNA or denatured DNA in reactions catalyzed by rat liver microsomes, no depurination adducts were detected. The profiles of stable adducts were similar both qualitatively and quantitatively with native or denatured DNA. With activation of BP by horseradish peroxidase, the profiles of stable adducts differed with native and denatured DNA. The total amount of adducts with denatured DNA was only 25% of the amount detected with native DNA. No depurination adducts were detected with denatured DNA or RNA in the peroxidase system. The results reported here demonstrate that in mouse skin BP-DNA adducts are predominantly formed by one-electron oxidation and that this mechanism of activation requires double helical DNA for formation of adducts. 24 refs., 6 figs., 2 tabs.

• DOE Contract Number: W-7405-ENG-82
• OSTI ID: 7026084
• Journal Information: Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 6:3; ISSN CRTOEC; ISSN 0893-228X
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AMINES
ANIMALS
AROMATICS
AZAARENES
BENZOPYRENE
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
BODY
CELL CONSTITUENTS
CONDENSED AROMATICS
DNA ADDUCTS
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
MAMMALS
MICE
MICROSOMES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PURINES
RIBOSOMES
RODENTS
SKIN
STRUCTURAL CHEMICAL ANALYSIS
SYNTHESIS
TOXICITY
VERTEBRATES