title: Multiclass Carcinogenic DNA Adduct Quantification in Formalin-Fixed Paraffin-Embedded Tissues by Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry.
abstract: DNA adducts are a measure of internal exposure to genotoxicants and an important biomarker for human risk assessment. However, the employment of DNA adducts as biomarkers in human studies is often restricted because fresh-frozen tissues are not available. In contrast, formalin-fixed paraffin-embedded (FFPE) tissues with clinical diagnosis are readily accessible. Recently, our laboratory reported that DNA adducts of aristolochic acid, a carcinogenic component of Aristolochia herbs used in traditional Chinese medicines worldwide, can be recovered quantitatively from FFPE tissues. In this study, we have evaluated the efficacy of our method for retrieval of DNA adducts from archived tissue by measuring DNA adducts derived from four other classes of human carcinogens: polycyclic aromatic hydrocarbons (PAHs), aromatic amines, heterocyclic aromatic amines (HAAs), and N-nitroso compounds (NOCs). Deoxyguanosine (dG) adducts of the PAH benzo[a]pyrene (B[a]P), 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (dG-N(2)-B[a]PDE); the aromatic amine 4-aminobiphenyl (4-ABP), N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-4-ABP); the HAA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), N-(deoxyguanosin-8-yl)-PhIP (dG-C8-PhIP); and the dG adducts of the NOC 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), O(6)-methyl-dG (O(6)-Me-dG) and O(6)-pyridyloxobutyl-dG (O(6)-POB-dG), formed in liver, lung, bladder, pancreas, or colon were recovered in comparable yields from fresh-frozen and FFPE preserved tissues of rodents treated with the procarcinogens. Quantification was achieved by ultraperformance liquid chromatography coupled with electrospray ionization ion-trap multistage mass spectrometry (UPLC/ESI-IT-MS(3)). These advancements in the technology of DNA adduct retrieval from FFPE tissue clear the way for use of archived pathology samples in molecular epidemiology studies designed to assess the causal role of exposure to hazardous chemicals with cancer risk.
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Pharmacological Sciences and ∥Department of Medicine, Stony Brook University , Stony Brook, New York 11794, United States.
authors.forename: Jingshu
authors.initials: J
authors.lastname: Guo
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Pharmacological Sciences and ∥Department of Medicine, Stony Brook University , Stony Brook, New York 11794, United States.
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Yun
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Pharmacological Sciences and ∥Department of Medicine, Stony Brook University , Stony Brook, New York 11794, United States.
authors.forename: Pramod
authors.initials: P
authors.lastname: Upadhyaya
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Pharmacological Sciences and ∥Department of Medicine, Stony Brook University , Stony Brook, New York 11794, United States.
authors.forename: Lihua
authors.initials: L
authors.lastname: Yao
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Pharmacological Sciences and ∥Department of Medicine, Stony Brook University , Stony Brook, New York 11794, United States.
authors.forename: Sesha
authors.initials: S
authors.lastname: Krishnamachari
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Pharmacological Sciences and ∥Department of Medicine, Stony Brook University , Stony Brook, New York 11794, United States.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rosenquist
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Pharmacological Sciences and ∥Department of Medicine, Stony Brook University , Stony Brook, New York 11794, United States.
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Grollman
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Pharmacological Sciences and ∥Department of Medicine, Stony Brook University , Stony Brook, New York 11794, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Turesky
mesh_terms: D000818:Animals; D030022:Aristolochia / Q000737:chemistry; D034341:Aristolochic Acids / Q000032:analysis*; D002273:Carcinogens / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000737:chemistry; D018736:DNA Adducts / Q000032:analysis*; D005260:Female; D005557:Formaldehyde / Q000737:chemistry*; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010179:Pancreas / Q000737:chemistry; D016612:Paraffin Embedding; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry; D001743:Urinary Bladder / Q000737:chemistry
chemical_list: D034341:Aristolochic Acids; D002273:Carcinogens; D018736:DNA Adducts; D005557:Formaldehyde; C000228:aristolochic acid I