title: Biological clues to potent DNA-damaging activities in food and flavoring.
abstract: Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51×) and etoposide (33×); flavonoids: EGCG (19×), curcumin (12×), apigenin (9×), and quercetin (7×); beverages: chamomile (11×), green (21×), and black tea (26×) and coffee (3-29×); and liquid smoke (4-28×). Damage occurred at dietary concentrations: etoposide near 5μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30×), 3-methoxycatechol (25×), gallic acid (21×), and 1,2,4-benzenetriol (21×). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets.
authors: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: M Zulfiquer
authors: MZ
authors: Hossain
authors: Samuel F
authors: SF
authors: Gilbert
authors: Kalpesh
authors: K
authors: Patel
authors: Soma
authors: S
authors: Ghosh
authors: Anil K
authors: AK
authors: Bhunia
authors: Scott E
authors: SE
authors: Kern
mesh_terms: D002460:Cell Line; D004249:DNA Damage; D005421:Flavoring Agents / Q000633:toxicity*; D005504:Food Analysis; D006801:Humans
chemical_list: D005421:Flavoring Agents
references: J Agric Food Chem. 2007 Nov 14;55(23):9470-8
references: 17939735
references: Cancer Res. 1989 Jan 1;49(1):164-8
references: 2908843
references: Carcinogenesis. 2005 Oct;26(10):1811-20
references: 15905198
references: Cancer Lett. 1981 Dec;14(3):251-60
references: 7199376
references: Mutat Res. 1981 Oct;90(2):91-109
references: 6799819
references: Cancer Res. 1993 Jan 1;53(1):32-7
references: 8416747
references: Jpn J Cancer Res. 1990 Sep;81(9):857-61
references: 2121686
references: PLoS One. 2011;6(6):e20456
references: 21674008
references: J Sci Food Agric. 1975 Mar;26(3):267-76
references: 1169662
references: Sci Transl Med. 2011 Aug 10;3(95):95ra74
references: 21832239
references: Cancer Biol Ther. 2003 Mar-Apr;2(2):196-202
references: 12750563
references: J Biomed Sci. 1994 Mar;1(2):125-130
references: 11725015
references: Food Chem Toxicol. 1989 Mar;27(3):193-203
references: 2731816
references: Chem Biol Interact. 1995 Dec 22;98(3):283-301
references: 8548865
references: Environ Mol Mutagen. 2011 Jun;52(5):339-54
references: 21538556
references: Chem Pharm Bull (Tokyo). 1997 May;45(5):888-93
references: 9178524
references: Br J Cancer. 1960 Mar;14:147-50
references: 14409278
references: Basic Res Cardiol. 2009 Jan;104(1):100-10
references: 19101751
references: Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11
references: 1933891
references: J Nat Prod. 2007 May;70(5):763-7
references: 17411092
references: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4790-5
references: 10758153
references: Molecules. 2008 Dec 04;13(12):2998-3006
references: 19052524
references: Regul Toxicol Pharmacol. 2009 Nov;55(2):188-99
references: 19591892
references: Mol Carcinog. 2008 Feb;47(2):114-25
references: 17620290
references: Chem Res Toxicol. 2008 Apr;21(4):936-43
references: 18293940
references: Clin Chem. 1978 Feb;24(2):362-4
references: 627073
references: Carcinogenesis. 1992 Apr;13(4):605-8
references: 1315626
references: J Agric Food Chem. 2006 Aug 9;54(16):5755-62
references: 16881674
references: Pharmacol Ther. 2001 May-Jun;90(2-3):157-77
references: 11578656
references: Carcinogenesis. 2002 Jun;23(6):949-57
references: 12082016
references: Mol Syst Biol. 2006;2:2006.0033
references: 16773083
references: Mutagenesis. 1998 May;13(3):271-4
references: 9643586
references: Food Chem Toxicol. 1989 Aug;27(8):511-6
references: 2792974
references: Food Chem Toxicol. 1987 Apr;25(4):331-5
references: 3556356
references: Acta Pharmacol Toxicol (Copenh). 1970;28(1):28-38
references: 5467752
references: Basic Life Sci. 1992;59:739-65
references: 1417698
references: J Nat Prod. 2007 Dec;70(12):1884-8
references: 18076140
references: Environ Health Perspect. 2010 Apr;118(4):485-92
references: 20368123
references: Cancer Biol Ther. 2005 Aug;4(8):893-8
references: 16177561
references: Nature. 2012 Feb 29;483(7387):S2-6
references: 22378123
references: Food Chem Toxicol. 1992 Sep;30(9):771-81
references: 1427515
references: Mutat Res. 2002 Jun 19;503(1-2):21-35
references: 12052500
references: Biotechnol J. 2010 Oct;5(10):1050-9
references: 20931601
references: J Agric Food Chem. 2006 Dec 27;54(26):9966-77
references: 17177529
references: J Agric Food Chem. 2006 Dec 27;54(26):10086-91
references: 17177545
references: Cancer Res. 1989 Sep 15;49(18):5111-7
references: 2548712
references: Mol Nutr Food Res. 2008 May;52(5):507-26
references: 18435439
references: J Agric Food Chem. 2005 Mar 9;53(5):1428-34
references: 15740018
references: Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17448-53
references: 16287968
references: Lancet. 1987 Aug 8;2(8554):327-8
references: 2886779
references: Nutr Cancer. 2008;60(2):131-44
references: 18444144
references: Food Chem Toxicol. 1992 Oct;30(10):859-64
references: 1427508
references: Mutagenesis. 2011 Jul;26(4):489-98
references: 21382914
references: J Infect Dis. 1978 Feb;137(2):122-30
references: 627734
references: Environ Health Perspect. 1989 Jul;82:81-9
references: 2676505
references: Cancer Res. 1999 Sep 1;59(17):4375-82
references: 10485486
references: Biochim Biophys Acta. 1997 Aug 29;1336(2):123-31
references: 9305782
references: Phytochemistry. 2000 Feb;53(3):391-4
references: 10703063
references: Biochem J. 1996 Jan 1;313 ( Pt 1):163-9
references: 8546678
references: Science. 1991 Jun 21;252(5013):1708-11
references: 2047879
references: J Natl Cancer Inst. 1976 Jul;57(1):207-9
references: 187761
references: Spectrochim Acta A Mol Biomol Spectrosc. 2009 Dec;74(5):1046-9
references: 19800839
references: Biotechniques. 2004 Jul;37(1):120-2
references: 15283209
references: Food Chem Toxicol. 1999 Nov;37(11):1113-8
references: 10566883