title: DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 4-aminobiphenyl are infrequently detected in human mammary tissue by liquid chromatography/tandem mass spectrometry.
abstract: Some epidemiological investigations have revealed that frequent consumption of well-done cooked meats and tobacco smoking are risk factors for breast cancer in women. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic aromatic amine that is formed in well-done cooked meat, and 4-aminobiphenyl (4-ABP) is an aromatic amine that arises in tobacco smoke and occurs as a contaminant in the atmosphere. Both compounds are rodent mammary carcinogens, and putative DNA adducts of PhIP and 4-ABP have been frequently detected, by immunohistochemistry (IHC) or (32)P-post-labeling methods, in mammary tissue of USA women. Because of these findings, PhIP and 4-ABP have been implicated as causal agents of human breast cancer. However, the biomarker data are controversial: both IHC and (32)P-post-labeling are non-selective screening methods and fail to provide confirmatory spectral data. Consequently, the identities of the lesions are equivocal. We employed a specific and sensitive liquid chromatography/mass spectrometry (MS) method, to screen tumor-adjacent normal mammary tissue for DNA adducts of PhIP and 4-ABP. Only 1 of 70 biopsy samples obtained from Minneapolis, Minnesota breast cancer patients contained a PhIP-DNA adduct. The level was three adducts per 10(9) nucleotides, a level that is 100-fold lower than the mean level of PhIP adducts reported by IHC or (32)P-post-labeling methods. The occurrence of 4-ABP-DNA adducts was nil in those same breast tissues. Our findings, derived from a specific mass spectrometry method, signify that PhIP and 4-ABP are not major DNA-damaging agents in mammary tissue of USA women and raise questions about the roles of these chemicals in breast cancer.
authors.affiliation: Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Gu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Turesky
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Tao
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Langouët
authors.forename: Gwendoline C
authors.initials: GC
authors.lastname: Nauwelaërs
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
authors.forename: Douglas
authors.initials: D
authors.lastname: Yee
authors.forename: Mimi C
authors.initials: MC
authors.lastname: Yu
mesh_terms: D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000209:etiology*; D002853:Chromatography, Liquid / Q000379:methods*; D018736:DNA Adducts / Q000032:analysis*; D004032:Diet; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000032:analysis*; D007150:Immunohistochemistry; D008460:Meat; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C502239:2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct; D000611:Aminobiphenyl Compounds; D018736:DNA Adducts; D007093:Imidazoles; C006757:4-biphenylamine
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Aug;17(8):2146-51
references.pmid: 18669582
references.citation: Chem Res Toxicol. 2011 Jun 20;24(6):913-25
references.pmid: 21456541
references.citation: Int J Cancer. 1998 Mar 16;75(6):825-30
references.pmid: 9506525
references.citation: Environ Mol Mutagen. 2002;39(2-3):134-42
references.pmid: 11921181
references.citation: Mutat Res. 2002 Sep 30;506-507:145-52
references.pmid: 12351154
references.citation: Carcinogenesis. 2000 Apr;21(4):607-15
references.pmid: 10753193
references.citation: Chem Res Toxicol. 2010 Jul 19;23(7):1234-44
references.pmid: 20443584
references.citation: Nat Rev Cancer. 2005 Dec;5(12):986-94
references.pmid: 16341086
references.citation: Cancer Epidemiol Biomarkers Prev. 2003 Jun;12(6):503-7
references.pmid: 12814994
references.citation: Chem Res Toxicol. 1992 Sep-Oct;5(5):585-90
references.pmid: 1445997
references.citation: Chem Res Toxicol. 2005 Apr;18(4):692-9
references.pmid: 15833029
references.citation: J Cancer Res Clin Oncol. 1990;116(5):499-502
references.pmid: 2229141
references.citation: Environ Mol Mutagen. 2002;39(2-3):184-92
references.pmid: 11921188
references.citation: Food Chem Toxicol. 1998 Apr;36(4):279-87
references.pmid: 9651044
references.citation: Cancer Res. 1998 Oct 1;58(19):4307-13
references.pmid: 9766658
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Mar 25;802(1):127-33
references.pmid: 15036004
references.citation: Cancer Epidemiol Biomarkers Prev. 1999 Sep;8(9):733-9
references.pmid: 10498391
references.citation: Int J Cancer. 2009 May 15;124(10):2430-5
references.pmid: 19165862
references.citation: Cancer Epidemiol Biomarkers Prev. 2001 Feb;10(2):89-94
references.pmid: 11219777
references.citation: Chemosphere. 2001 Feb-Mar;42(5-7):473-9
references.pmid: 11219671
references.citation: Environ Mol Mutagen. 2002;39(2-3):143-9
references.pmid: 11921182
references.citation: IARC Monogr Eval Carcinog Risks Hum. 1991;52:1-544
references.pmid: 1683674
references.citation: Chem Res Toxicol. 2007 Feb;20(2):263-76
references.pmid: 17305409
references.citation: Chem Res Toxicol. 1999 Jan;12(1):78-82
references.pmid: 9894021
references.citation: Chem Res Toxicol. 2003 Sep;16(9):1162-73
references.pmid: 12971805
references.citation: Cancer Epidemiol Biomarkers Prev. 1995 Apr-May;4(3):233-8
references.pmid: 7606197
references.citation: Cancer Sci. 2004 Apr;95(4):290-9
references.pmid: 15072585
references.citation: Carcinogenesis. 2007 Feb;28(2):342-9
references.pmid: 16926175
references.citation: Chem Res Toxicol. 1992 Sep-Oct;5(5):691-7
references.pmid: 1446011
references.citation: Environ Pollut. 1993;80(3):281-6
references.pmid: 15091848
references.citation: Carcinogenesis. 2003 Apr;24(4):719-25
references.pmid: 12727801
references.citation: Nutr Cancer. 2009;61(4):437-46
references.pmid: 19838915
references.citation: Cancer Epidemiol Biomarkers Prev. 1997 Aug;6(8):573-81
references.pmid: 9264269
references.citation: Int J Cancer. 1999 Jan 5;80(1):13-7
references.pmid: 9935222
references.citation: Breast Cancer Res Treat. 2002 Jun;74(3):235-54
references.pmid: 12206514
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):15-26
references.pmid: 18187392
references.citation: IARC Sci Publ. 1993;(124):11-23
references.pmid: 8225473
references.citation: Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):953-71
references.pmid: 12376493
references.citation: Chem Res Toxicol. 1999 Jan;12(1):68-77
references.pmid: 9894020
references.citation: Int J Cancer. 2002 Jun 10;99(5):747-50
references.pmid: 12115511
references.citation: Mutagenesis. 2009 Mar;24(2):127-32
references.pmid: 18980957
references.citation: Cancer Epidemiol Biomarkers Prev. 2003 Sep;12(9):830-7
references.pmid: 14504191
references.citation: Chem Res Toxicol. 2011 Aug 15;24(8):1169-214
references.pmid: 21688801
references.citation: Cancer Detect Prev. 1999;23(6):454-62
references.pmid: 10571655
references.citation: Chem Res Toxicol. 1995 Jul-Aug;8(5):747-52
references.pmid: 7548758
references.citation: J Natl Cancer Inst. 1998 Nov 18;90(22):1687-9
references.pmid: 9827516
references.citation: Mutat Res. 2000 Dec 20;472(1-2):119-27
references.pmid: 11113704