title: Biomonitoring DNA Adducts of Cooked Meat Carcinogens in Human Prostate by Nano Liquid Chromatography-High Resolution Tandem Mass Spectrometry: Identification of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine DNA Adduct.
abstract: Epidemiologic studies have reported an association between frequent consumption of well-done cooked meats and prostate cancer risk. However, unambiguous physiochemical markers of DNA damage from carcinogens derived from cooked meats, such as DNA adducts, have not been identified in human samples to support this paradigm. We have developed a highly sensitive nano-LC-Orbitrap MSnmethod to measure DNA adducts of several carcinogens originating from well-done cooked meats, tobacco smoke, and environmental pollution, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-9H-pyrido[2,3-b]indole (AαC), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), benzo[a]pyrene (B[a]P), and 4-aminobiphenyl (4-ABP). The limit of quantification (LOQ) of the major deoxyguanosine (dG) adducts of these carcinogens ranged between 1.3 and 2.2 adducts per 109nucleotides per 2.5 μg of DNA assayed. The DNA adduct of PhIP, N-(deoxyguanosin-8-yl)-PhIP (dG-C8-PhIP) was identified in 11 out of 35 patients, at levels ranging from 2 to 120 adducts per 109nucleotides. The dG-C8 adducts of AαC and MeIQx, and the B[a]P adduct, 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (dG-N2-B[a]PDE) were not detected in any specimen, whereas N-(deoxyguanosin-8-yl)-4-ABP (dG-C8-4-ABP) was identified in one subject (30 adducts per 109nucleotides). PhIP-DNA adducts also were recovered quantitatively from formalin fixed paraffin embedded (FFPE) tissues, signifying FFPE tissues can serve as biospecimens for carcinogen DNA adduct biomarker research. Our biomarker data provide support to the epidemiological observations implicating PhIP, one of the most mass-abundant heterocyclic aromatic amines formed in well-done cooked meats, as a DNA-damaging agent that may contribute to the etiology of prostate cancer.
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Laboratory Medicine and Pathology and ∥Department of Urology, University of Minnesota , 420 Delaware Street SE, Minneapolis, Minnesota 55455, United States.
authors.forename: Shun
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Laboratory Medicine and Pathology and ∥Department of Urology, University of Minnesota , 420 Delaware Street SE, Minneapolis, Minnesota 55455, 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 Laboratory Medicine and Pathology and ∥Department of Urology, University of Minnesota , 420 Delaware Street SE, Minneapolis, Minnesota 55455, 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 Laboratory Medicine and Pathology and ∥Department of Urology, University of Minnesota , 420 Delaware Street SE, Minneapolis, Minnesota 55455, United States.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Villalta
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Laboratory Medicine and Pathology and ∥Department of Urology, University of Minnesota , 420 Delaware Street SE, Minneapolis, Minnesota 55455, United States.
authors.forename: Suprita
authors.initials: S
authors.lastname: Krishna
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Laboratory Medicine and Pathology and ∥Department of Urology, University of Minnesota , 420 Delaware Street SE, Minneapolis, Minnesota 55455, United States.
authors.forename: Resha
authors.initials: R
authors.lastname: Tejpaul
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Laboratory Medicine and Pathology and ∥Department of Urology, University of Minnesota , 420 Delaware Street SE, Minneapolis, Minnesota 55455, United States.
authors.forename: Paari
authors.initials: P
authors.lastname: Murugan
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Laboratory Medicine and Pathology and ∥Department of Urology, University of Minnesota , 420 Delaware Street SE, Minneapolis, Minnesota 55455, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Weight
authors.affiliation: Masonic Cancer Center and ‡Department of Medicinal Chemistry, University of Minnesota , 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.|Department of Laboratory Medicine and Pathology and ∥Department of Urology, University of Minnesota , 420 Delaware Street SE, Minneapolis, Minnesota 55455, United States.
authors.forename: Robert J
authors.identifier: 0000-0001-7355-9903
authors.initials: RJ
authors.lastname: Turesky
mesh_terms: D000368:Aged; D000818:Animals; D002273:Carcinogens / Q000032:analysis*; D002417:Cattle; D002853:Chromatography, Liquid / Q000379:methods*; D003296:Cooking; D018736:DNA Adducts / Q000032:analysis*; D006801:Humans; D007093:Imidazoles / Q000032:analysis*; D057230:Limit of Detection; D008297:Male; D008460:Meat / Q000032:analysis; D008875:Middle Aged; D011467:Prostate / Q000737:chemistry*; D011810:Quinoxalines / Q000032:analysis; D012906:Smoke / Q000032:analysis; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C502239:2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct; D002273:Carcinogens; D018736:DNA Adducts; D007093:Imidazoles; D011810:Quinoxalines; D012906:Smoke; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine