title: In vitro characterization of DNA adducts formed by foundry air particulate matter.
abstract: This study is part of an ongoing investigation of biomarkers in iron foundry workers exposed to polycyclic aromatic compounds. Foundry workers with the highest exposures had elevated levels of DNA adducts in their white blood cells in previous studies. The purpose of this study was to characterize the nature of DNA reactive chemicals in foundry air samples through incubating the foundry filter extract with DNA and activation enzymes. Calf thymus DNA was incubated with foundry filter extract and activated by either rat liver activation mixture (S9 mix) or xanthine oxidase. A complex pattern of adducts was observed on thin-layer chromatography (TLC) by the 32P-postlabeling assay. Two selected polycyclic aromatic hydrocarbons (PAHs)--1-NP-and anti(+/-)benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide [anti(+/-) BPDE]-DNA adducts--were used as marker compounds in characterizing the postlabeled DNA adducts by TLC combined with high-performance liquid chromatography (HPLC). After an initial separation of DNA adducts by TLC, individual spots were isolated and separated further on HPLC. HPLC analysis and spiking with anti(+/-)BPDE-DNA standard confirmed the co-migration of the anti(+/-)BPDE-DNA standard with one PAH adduct formed by the S9 mix-activated DCM extract in calf thymus DNA.
authors.affiliation: Institute of Occupational Health, Molecular Dosimetry Group, Helsinki, Finland. ksav@occuphealth.fi
authors.forename: K
authors.initials: K
authors.lastname: Savela
authors.forename: M J
authors.initials: MJ
authors.lastname: Kohan
authors.forename: D
authors.initials: D
authors.lastname: Walsh
authors.forename: F P
authors.initials: FP
authors.lastname: Perera
authors.forename: K
authors.initials: K
authors.lastname: Hemminki
authors.forename: J
authors.initials: J
authors.lastname: Lewtas
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis; D016902:Air Pollution, Indoor; D000818:Animals; D001564:Benzo(a)pyrene / Q000032:analysis; D015415:Biomarkers; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D018736:DNA Adducts / Q000032:analysis*; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron; D007962:Leukocytes / Q000737:chemistry / Q000187:drug effects; D008669:Metallurgy; D016273:Occupational Exposure; D010761:Phosphorus Radioisotopes; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis*; D011721:Pyrenes / Q000032:analysis / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; C095911:polycyclic aromatic hydrocarbons-DNA adduct; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D007501:Iron; C032668:1-nitropyrene