title: Characterization of DNA adducts in Chinese hamster ovary cells treated with mutagenic doses of 1- and 3-nitrosobenzo[a]pyrene and the trans-7,8-diol-anti-9,10-epoxides of 1- and 3-nitrobenzo[a]pyrene.
abstract: The environmental contaminants 1- and 3-nitrobenzo[a]pyrene (1- and 3-nitro-BaP) are mutagens in Chinese hamster ovary (CHO) cells with exogenous metabolic activation. Previous studies demonstrated the potent direct-acting mutagenicity of the oxidized metabolites, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-1-nitrobenzo[a] pyrene (1-NBaPDE) and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9, 10-tetrahydro-3-nitrobenzo[a]pyrene (3-NBaPDE), and the partially nitroreduced metabolites, 1- and 3-nitrosobenzo[a]pyrene (1- and 3-NO-BaP). In this study, we have identified the major adduct formed by incubation of calf thymus DNA with 1-NBaPDE and used this standard in conjunction with other adduct standards to characterize the 32P-postlabeled DNA adducts produced by 1- and 3-nitro-BaP metabolites in CHO cultures. The major adduct from 1-NBaPDE exposure was 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-1- nitrobenzo[a]pyrene; from 3-NBaPDE, 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-3- nitrobenzo[a]pyrene; from 1-NO-BaP, 6-(deoxyguanosin-N2-yl)-1-aminobenzo[a]pyrene; and from 3-NO-BaP, 6-(deoxyguanosin-N2-yl)-3-aminobenzo[a]pyrene. For comparison, the adducts formed by trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and the related nitroreduced derivative 6-nitrosobenzo[a]pyrene were also examined. The nitrobenzo[a]pyrene DNA adducts described in this study are proposed to be involved in the mutagenicity of 1- and 3-nitro-BaP upon either oxidative or reductive metabolism.
authors.affiliation: Department of Health and Human Services, Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR 72079, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Zhan
authors.forename: L H
authors.initials: LH
authors.lastname: Chiu
authors.forename: L S
authors.initials: LS
authors.lastname: Von Tungeln
authors.forename: D
authors.initials: D
authors.lastname: Herreno-Saenz
authors.forename: E
authors.initials: E
authors.lastname: Cheng
authors.forename: F E
authors.initials: FE
authors.lastname: Evans
authors.forename: R H
authors.initials: RH
authors.lastname: Heflich
authors.forename: P P
authors.initials: PP
authors.lastname: Fu
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D001580:Benzopyrenes / Q000633:toxicity*; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D004247:DNA / Q000187:drug effects / Q000302:isolation & purification; D018736:DNA Adducts / Q000737:chemistry* / Q000187:drug effects; D003854:Deoxyribonucleotides / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity; D009153:Mutagens; D010761:Phosphorus Radioisotopes; D013950:Thymus Gland
chemical_list: C018502:2'-deoxyribonucleoside 3',5'-bisphosphate; D001580:Benzopyrenes; D018736:DNA Adducts; D003854:Deoxyribonucleotides; D004785:Environmental Pollutants; D009153:Mutagens; D010761:Phosphorus Radioisotopes; C085532:3-nitrobenzo(a)pyrene-7,8-diol-9,10-epoxide; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C042055:3-nitrobenzo(a)pyrene; C040217:1-nitrobenzo(a)pyrene; D004247:DNA