Identification and characterization of a novel benzo[a]pyrene-derived DNA adduct.
The aim of this study was to generate and identify a novel benzo[a]pyrene (BP)-derived DNA adduct found both in vitro and in vivo. To date, the majority of studies have focused on N(2)-[10 beta(7 beta,8a,9a-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene)yl]-deoxyguanosine (anti-BPDE-dG), the major adduct generated following bioactivation of BP. However, a second adduct is also formed following bioactivation of BP which has been speculated to result from further metabolism of 9-OH-BP. In order to identify this second reaction pathway, the ultimate DNA binding species, and the DNA base involved, we have synthesized and characterized a dG-derived DNA adduct arising from further bioactivation of 9-OH-BP in the presence of rat liver microsomes. Analysis of the adducted nucleotides was conducted using both the (32)P-postlabeling assay and capillary electrophoresis-mass spectrometry (CE-MS).
Fang
A H
AH
Barnett Institute and Department of Chemistry, Northeastern University, Boston, Massachusetts 02115, USA.
Smith
W A
WA
Vouros
P
P
Gupta
R C
RC
D000818:Animals; D001564:Benzo(a)pyrene / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D004247:DNA / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D008862:Microsomes, Liver / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland
D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D001564:Benzo(a)pyrene; D004247:DNA