Skip to main content
×
Home
    • Aa
    • Aa

Use of conventional and -omics based methods for health claims of dietary antioxidants: a critical overview

  • Siegfried Knasmüller (a1), Armen Nersesyan (a1), Miroslav Mišík (a1), Christopher Gerner (a1), Wolfgang Mikulits (a1), Veronika Ehrlich (a1), Christine Hoelzl (a1), Akos Szakmary (a1) and Karl-Heinz Wagner (a2)...
Abstract

This article describes the principles and limitations of methods used to investigate reactive oxygen species (ROS) protective properties of dietary constituents and is aimed at providing a better understanding of the requirements for science based health claims of antioxidant (AO) effects of foods. A number of currently used biochemical measurements aimed of determining the total antioxidant capacity and oxidised lipids and proteins are carried out under unphysiologcial conditions and are prone to artefact formation. Probably the most reliable approaches are measurements of isoprostanes as a parameter of lipid peroxidation and determination of oxidative DNA damage. Also the design of the experimental models has a strong impact on the reliability of AO studies: the common strategy is the identification of AO by in vitro screening with cell lines. This approach is based on the assumption that protection towards ROS is due to scavenging, but recent findings indicate that activation of transcription factors which regulate genes involved in antioxidant defence plays a key role in the mode of action of AO. These processes are not adequately represented in cell lines. Another shortcoming of in vitro experiments is that AO are metabolised in vivo and that most cell lines are lacking enzymes which catalyse these reactions. Compounds with large molecular configurations (chlorophylls, anthocyans and polyphenolics) are potent AO in vitro, but weak or no effects were observed in animal/human studies with realistic doses as they are poorly absorbed. The development of -omics approaches will improve the scientific basis for health claims. The evaluation of results from microarray and proteomics studies shows that it is not possible to establish a general signature of alterations of transcription and protein patterns by AO. However, it was shown that alterations of gene expression and protein levels caused by experimentally induced oxidative stress and ROS related diseases can be normalised by dietary AO.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Use of conventional and -omics based methods for health claims of dietary antioxidants: a critical overview
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Use of conventional and -omics based methods for health claims of dietary antioxidants: a critical overview
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Use of conventional and -omics based methods for health claims of dietary antioxidants: a critical overview
      Available formats
      ×
Copyright
Corresponding author
*Corresponding author: Professor Siegfried Knasmüller, fax +431 4277 9651, email siegfried.knasmueller@mediuniwien.ac.at
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1 R Blomhoff (2005) Dietary antioxidants and cardiovascular disease. Curr Opin Lipidol 16, 4754.

2 MM Elahi & BM Matata (2006) Free radicals in blood: evolving concepts in the mechanism of ischemic heart disease. Arch Biochem Biophys 450, 7888.

3 DJ Lefer & DN Granger (2000) Oxidative stress and cardiac disease. Am J Med 109, 315323.

4 A Agarwal , RK Sharma , KP Nallella , AJ Thomas Jr, JG Alvarez & SC Sikka (2006) Reactive oxygen species as an independent marker of male factor infertility. Fertil Steril 86, 878885.

7 T Yan , S Li , X Jiang & LW Oberley (1999) Altered levels of primary antioxidant enzymes in progeria skin fibroblasts. Biochem Biophys Res Commun 257, 163167.

8 R Kohen & A Nyska (2002) Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol 30, 620650.

9 RW Gracy , JM Talent , Y Kong & CC Conrad (1999) Reactive oxygen species: the unavoidable environmental insult? Mutat Res 428, 1722.

12 L Sarma & PC Kesavan (1993) Protective effects of vitamins C and E against gamma-ray-induced chromosomal damage in mouse. Int J Radiat Biol 63, 759764.

14 L Li , R Tsao , R Yang , C Liu , H Zhu & JC Young (2006) Polyphenolic profiles and antioxidant activities of heartnut (Juglans ailanthifolia Var. cordiformis) and Persian walnut (Juglans regia L.). J Agric Food Chem 54, 80338040.

15 MA Anagnostopoulou , P Kefalas , E Kokkalou , AN Assimopoulou & VP Papageorgiou (2005) Analysis of antioxidant compounds in sweet orange peel by HPLC–diode array detection–electrospray ionization mass spectrometry. Biomed Chromatogr 19, 138148.

16 M Minoggio , L Bramati , P Simonetti , C Gardana , L Iemoli , E Santangelo , PL Mauri , P Spigno , GP Soressi & PG Pietta (2003) Polyphenol pattern and antioxidant activity of different tomato lines and cultivars. Ann Nutr Metab 47, 6469.

18 JM Kim , HJ Chang , WK Kim , N Chang & HS Chun (2006) Structure–activity relationship of neuroprotective and reactive oxygen species scavenging activities for allium organosulfur compounds. J Agric Food Chem 54, 65476553.

19 K Iwai , N Kishimoto , Y Kakino , K Mochida & T Fujita (2004) In vitro antioxidative effects and tyrosinase inhibitory activities of seven hydroxycinnamoyl derivatives in green coffee beans. J Agric Food Chem 52, 48934898.

20 K Fujioka & T Shibamoto (2006) Quantitation of volatiles and nonvolatile acids in an extract from coffee beverages: correlation with antioxidant activity. J Agric Food Chem 54, 60546058.

21 M Lopez-Velez , F Martinez-Martinez & C Del Valle-Ribes (2003) The study of phenolic compounds as natural antioxidants in wine. Crit Rev Food Sci Nutr 43, 233244.

22 FJ Hidalgo , MM Leon & R Zamora (2006) Antioxidative activity of amino phospholipids and phospholipid/amino acid mixtures in edible oils as determined by the Rancimat method. J Agric Food Chem 54, 54615467.

23 A Luximon-Ramma , VS Neergheen , T Bahorun , A Crozier , V Zbarsky , KP Datla , DT Dexter & OI Aruoma (2006) Assessment of the polyphenolic composition of the organic extracts of Mauritian black teas: a potential contributor to their antioxidant functions. Biofactors 27, 7991.

24 GF Antonious , TS Kochhar , RL Jarret & JC Snyder (2006) Antioxidants in hot pepper: variation among accessions. J Environ Sci Health B 41, 12371243.

25 Y Masuda , H Kikuzaki , M Hisamoto & N Nakatani (2004) Antioxidant properties of gingerol related compounds from ginger. Biofactors 21, 293296.

26 P Somparn , C Phisalaphong , S Nakornchai , S Unchern & NP Morales (2007) Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biol Pharm Bull 30, 7478.

27 CY Hsu , CM Yang , CM Chen , PY Chao & SP Hu (2005) Effects of chlorophyll-related compounds on hydrogen peroxide induced DNA damage within human lymphocytes. J Agric Food Chem 53, 27462750.

28 S Xiong , LD Melton , AJ Easteal & D Siew (2006) Stability and antioxidant activity of black currant anthocyanins in solution and encapsulated in glucan gel. J Agric Food Chem 54, 62016208.

29 RD Semba , F Lauretani & L Ferrucci (2007) Carotenoids as protection against sarcopenia in older adults. Arch Biochem Biophys 458, 141145.

30 OI Aruoma , B Sun , H Fujii , VS Neergheen , T Bahorun , KS Kang & MK Sung (2006) Low molecular proanthocyanidin dietary biofactor Oligonol: its modulation of oxidative stress, bioefficacy, neuroprotection, food application and chemoprevention potentials. Biofactors 27, 245265.

31 BA Narayanan (2006) Chemopreventive agents alters global gene expression pattern: predicting their mode of action and targets. Curr Cancer Drug Targets 6, 711727.

32 A Abdelwahed , I Bouhlel , I Skandrani , K Valenti , M Kadri , P Guiraud , R Steiman , AM Mariotte , K Ghedira , F Laporte , MG Dijoux-Franca & L Chekir-Ghedira (2007) Study of antimutagenic and antioxidant activities of gallic acid and 1,2,3,4,6-pentagalloylglucose from Pistacia lentiscus. Confirmation by microarray expression profiling. Chem Biol Interact 165, 113.

33 JG Scandalios (2002) Oxidative stress responses – what have genome-scale studies taught us? Genome Biol 3, 1019.

34 E Choe & DB Min (2006) Chemistry and reactions of reactive oxygen species in foods. Crit Rev Food Sci Nutr 46, 122.

35 M Foksinski , D Gackowski , R Rozalski , A Siomek , J Guz , A Szpila , T Dziaman & R Olinski (2007) Effects of basal level of antioxidants on oxidative DNA damage in humans. Eur J Nutr 46, 174180.

36 P Karihtala & Y Soini (2007) Reactive oxygen species and antioxidant mechanisms in human tissues and their relation to malignancies. Apmis 115, 81103.

37 I Fridovich (1986) Biological effects of the superoxide radical. Arch Biochem Biophys 247, 111.

38 B Halliwell & JM Gutteridge (1999) Free Radicals in Biology and Medicine, 3rd ed.Avon, England: Oxford University Press.

40 G Czapski & S Goldstein (1995) The role of the reactions of NO with superoxide and oxygen in biological systems: a kinetic approach. Free Radic Biol Med 19, 785794.

41 OI Shadyro , IL Yurkova & MA Kisel (2002) Radiation-induced peroxidation and fragmentation of lipids in a model membrane. Int J Radiat Biol 78, 211217.

42 AP Pentland (1994) Active oxygen mechanisms of UV inflammation. Adv Exp Med Biol 366, 8797.

43 HS Koren (1995) Associations between criteria air pollutants and asthma. Environ Health Perspect 103, Suppl. 6, 235242.

44 K Victorin (1994) Review of the genotoxicity of nitrogen oxides. Mutat Res 317, 4355.

45 TW Yu & D Anderson (1997) Reactive oxygen species-induced DNA damage and its modification: a chemical investigation. Mutat Res 379, 201210.

46 A Wiseman , T Ridgway , PS Goldfarb & L Woods (2002) Are food and environmental toxicants ‘overdetected’ by bioassays? Trends Biotechnol 20, 1315.

49 J Kanner & T Lapidot (2001) The stomach as a bioreactor: dietary lipid peroxidation in the gastric fluid and the effects of plant-derived antioxidants. Free Radic Biol Med 31, 13881395.

50 C Richter , V Gogvadze , R Laffranchi , R Schlapbach , M Schweizer , M Suter , P Walter & M Yaffee (1995) Oxidants in mitochondria: from physiology to diseases. Biochim Biophys Acta 1271, 6774.

51 C Fleury , B Mignotte & JL Vayssiere (2002) Mitochondrial reactive oxygen species in cell death signaling. Biochimie 84, 131141.

52 NS Dhalla , RM Temsah & T Netticadan (2000) Role of oxidative stress in cardiovascular diseases. J Hypertens 18, 655673.

54 CL Hawkins , BE Brown & MJ Davies (2001) Hypochlorite- and hypobromite-mediated radical formation and its role in cell lysis. Arch Biochem Biophys 395, 137145.

55 MR Rodrigues , D Rodriguez , L Henrique Catalani , M Russo & A Campa (2003) Interferon-gamma independent oxidation of melatonin by macrophages. J Pineal Res 34, 6974.

58 RL Levine & ER Stadtman (2001) Oxidative modification of proteins during aging. Exp Gerontol 36, 14951502.

59 ER Stadtman (2004) Role of oxidant species in aging. Curr Med Chem 11, 11051112.

60 Y Kushnareva , AN Murphy & A Andreyev (2002) Complex I-mediated reactive oxygen species generation: modulation by cytochrome c and NAD(P)+ oxidation–reduction state. Biochem J 368, 545553.

61 GL Squadrito & WA Pryor (1998) Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide. Free Radic Biol Med 25, 392403.

62 M Younes & CP Siegers (1984) Interrelation between lipid peroxidation and other hepatotoxic events. Biochem Pharmacol 33, 20012003.

63 AA Horton & S Fairhurst (1987) Lipid peroxidation and mechanisms of toxicity. Crit Rev Toxicol 18, 2779.

65 JS Forrester & PK Shah (2006) Emerging strategies for increasing high-density lipoprotein. Am J Cardiol 98, 15421549.

66 P Moller & H Wallin (1998) Adduct formation, mutagenesis and nucleotide excision repair of DNA damage produced by reactive oxygen species and lipid peroxidation product. Mutat Res 410, 271290.

67 A Barzilai & K Yamamoto (2004) DNA damage responses to oxidative stress. DNA Repair (Amst) 3, 11091115.

68 JC Niles , JS Wishnok & SR Tannenbaum (2006) Peroxynitrite-induced oxidation and nitration products of guanine and 8-oxoguanine: structures and mechanisms of product formation. Nitric Oxide 14, 109121.

69 H Tsutsui , T Ide & S Kinugawa (2006) Mitochondrial oxidative stress, DNA damage, and heart failure. Antioxid Redox Signal 8, 17371744.

70 CE Vaca , J Wilhelm & M Harms-Ringdahl (1988) Interaction of lipid peroxidation products with DNA. A review. Mutat Res 195, 137149.

71 L Ehrenberg , S Osterman-Golkar , D Segerbck , K Svensson & CJ Calleman (1977) Evaluation of genetic risks of alkylating agents. III. Alkylation of haemoglobin after metabolic conversion of ethene to ethene oxide in vivo. Mutat Res 45, 175184.

72 D Segerback (1983) Alkylation of DNA and hemoglobin in the mouse following exposure to ethene and ethene oxide. Chem Biol Interact 45, 139151.

73 S Doublie , V Bandaru , JP Bond & SS Wallace (2004) The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity. Proc Natl Acad Sci U S A 101, 1028410289.

74 RJ Sanderson , SE Bennett , JS Sung & DW Mosbaugh (2001) Uracil-initiated base excision DNA repair synthesis fidelity in human colon adenocarcinoma LoVo and Escherichia coli cell extracts. Prog Nucleic Acid Res Mol Biol 68, 165188.

75 HE Krokan , F Drablos & G Slupphaug (2002) Uracil in DNA – occurrence, consequences and repair. Oncogene 21, 89358948.

76 MS Cooke , MD Evans , M Dizdaroglu & J Lunec (2003) Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 17, 11951214.

77 KS Kim , YJ Chang , YJ Chung , CU Park & HY Seo (2007) Enhanced expression of high-affinity iron transporters via H-ferritin production in yeast. J Biochem Mol Biol 40, 8287.

78 M Valko , CJ Rhodes , J Moncol , M Izakovic & M Mazur (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160, 140.

79 TP Dalton , HG Shertzer & A Puga (1999) Regulation of gene expression by reactive oxygen. Annu Rev Pharmacol Toxicol 39, 67101.

80 RG Allen & M Tresini (2000) Oxidative stress and gene regulation. Free Radic Biol Med 28, 463499.

81 JL Martindale & NJ Holbrook (2002) Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 192, 115.

82 J Mathers , JA Fraser , M McMahon , RD Saunders , JD Hayes & LI McLellan (2004) Antioxidant and cytoprotective responses to redox stress. Biochem Soc Symp, 157176.

83 ED Owuor & AN Kong (2002) Antioxidants and oxidants regulated signal transduction pathways. Biochem Pharmacol 64, 765770.

84 M Valko , D Leibfritz , J Moncol , MT Cronin , M Mazur & J Telser (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39, 4484.

85 Q Ma , L Battelli & AF Hubbs (2006) Multiorgan autoimmune inflammation, enhanced lymphoproliferation, and impaired homeostasis of reactive oxygen species in mice lacking the antioxidant-activated transcription factor Nrf2. Am J Pathol 168, 19601974.

86 G Poli , G Leonarduzzi , F Biasi & E Chiarpotto (2004) Oxidative stress and cell signalling. Curr Med Chem 11, 11631182.

87 J Abe & BC Berk (1999) Fyn and JAK2 mediate Ras activation by reactive oxygen species. J Biol Chem 274, 2100321010.

88 F Esposito , G Chirico , N Montesano Gesualdi , I Posadas , R Ammendola , T Russo , G Cirino & F Cimino (2003) Protein kinase B activation by reactive oxygen species is independent of tyrosine kinase receptor phosphorylation and requires SRC activity. J Biol Chem 278, 2082820834.

89 R Gopalakrishna & S Jaken (2000) Protein kinase C signaling and oxidative stress. Free Radic Biol Med 28, 13491361.

91 M Lopez-Ilasaca , P Crespo , PG Pellici , JS Gutkind & R Wetzker (1997) Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase gamma. Science 275, 394397.

92 KE Iles & HJ Forman (2002) Macrophage signaling and respiratory burst. Immunol Res 26, 95105.

93 M Torres & HJ Forman (1999) Activation of several MAP kinases upon stimulation of rat alveolar macrophages: role of the NADPH oxidase. Arch Biochem Biophys 366, 231239.

94 A Rao , C Luo & PG Hogan (1997) Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 15, 707747.

96 KI Amiri & A Richmond (2005) Role of nuclear factor-kappa B in melanoma. Cancer Metastasis Rev 24, 301313.

97 LJ Hofseth , SP Hussain & CC Harris (2004) P53: 25 years after its discovery. Trends Pharmacol Sci 25, 177181.

98 HO Jin , S An , HC Lee , SH Woo , SK Seo , TB Choe , DH Yoo , SB Lee , HD Um , SJ Lee , MJ Park , JI Kim , SI Hong , CH Rhee & IC Park (2007) Hypoxic condition- and high cell density-induced expression of Redd1 is regulated by activation of hypoxia-inducible factor-1alpha and Sp1 through the phosphatidylinositol 3-kinase/Akt signalling pathway. Cell Signal 19, 13931403.

99 MH Li , JH Jang & YJ Surh (2005) Nitric oxide induces apoptosis via AP-1-driven upregulation of COX-2 in rat pheochromocytoma cells. Free Radic Biol Med 39, 890899.

100 AA Sablina , AV Budanov , GV Ilyinskaya , LS Agapova , JE Kravchenko & PM Chumakov (2005) The antioxidant function of the p53 tumor suppressor. Nat Med 11, 13061313.

102 S Jauliac , C Lopez-Rodriguez , LM Shaw , LF Brown , A Rao & A Toker (2002) The role of NFAT transcription factors in integrin-mediated carcinoma invasion. Nat Cell Biol 4, 540544.

104 HC Huang , T Nguyen & CB Pickett (2000) Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2. Proc Natl Acad Sci USA 97, 1247512480.

105 T Nguyen , CS Yang & CB Pickett (2004) The pathways and molecular mechanisms regulating Nrf2 activation in response to chemical stress. Free Radic Biol Med 37, 433441.

106 LV Favreau & CB Pickett (1995) The rat quinone reductase antioxidant response element. Identification of the nucleotide sequence required for basal and inducible activity and detection of antioxidant response element-binding proteins in hepatoma and non-hepatoma cell lines. J Biol Chem 270, 2446824474.

108 JE Klaunig & LM Kamendulis (2004) The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 44, 239267.

109 C Michiels , M Raes , O Toussaint & J Remacle (1994) Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic Biol Med 17, 235248.

111 MK Kwak , N Wakabayashi , K Itoh , H Motohashi , M Yamamoto & TW Kensler (2003) Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival. J Biol Chem 278, 81358145.

113 M McMahon , K Itoh , M Yamamoto & JD Hayes (2003) Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J Biol Chem 278, 2159221600.

114 K Itoh , N Wakabayashi , Y Katoh , T Ishii , K Igarashi , JD Engel & M Yamamoto (1999) Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev 13, 7686.

115 MK Kwak & TW Kensler (2006) Induction of 26S proteasome subunit PSMB5 by the bifunctional inducer 3-methylcholanthrene through the Nrf2-ARE, but not the AhR/Arnt-XRE, pathway. Biochem Biophys Res Commun 345, 13501357.

116 X He , GX Lin , MG Chen , JX Zhang & Q Ma (2007) Protection against chromium (VI)-induced oxidative stress and apoptosis by Nrf2. Recruiting Nrf2 into the nucleus and disrupting the nuclear Nrf2/Keap1 association. Toxicol Sci 98, 298309.

117 X He , MG Chen , GX Lin & Q Ma (2006) Arsenic induces NAD(P)H-quinone oxidoreductase I by disrupting the Nrf2 × Keap1 × Cul3 complex and recruiting Nrf2 × Maf to the antioxidant response element enhancer. J Biol Chem 281, 2362023631.

119 JK Kundu & YJ Surh (2005) Breaking the relay in deregulated cellular signal transduction as a rationale for chemoprevention with anti-inflammatory phytochemicals. Mutat Res 591, 123146.

120 C Chen & AN Kong (2004) Dietary chemopreventive compounds and ARE/EpRE signaling. Free Radic Biol Med 36, 15051516.

122 EF Stange (2006) Review Article: the effect of aminosalicylates and immunomodulation on cancer risk in inflammatory bowel disease. Aliment Pharmacol Ther 24, Suppl. 3, 6467.

123 VM Chia , PA Newcomb , J Bigler , LM Morimoto , SN Thibodeau & JD Potter (2006) Risk of microsatellite-unstable colorectal cancer is associated jointly with smoking and nonsteroidal anti-inflammatory drug use. Cancer Res 66, 68776883.

124 AN Kong , E Owuor , R Yu , V Hebbar , C Chen , R Hu & S Mandlekar (2001) Induction of xenobiotic enzymes by the MAP kinase pathway and the antioxidant or electrophile response element (ARE/EpRE). Drug Metab Rev 33, 255271.

125 T Nishinaka , Y Ichijo , M Ito , M Kimura , M Katsuyama , K Iwata , T Miura , T Terada & C Yabe-Nishimura (2007) Curcumin activates human glutathione S-transferase P1 expression through antioxidant response element. Toxicol Lett 170, 238247.

126 S Tanigawa , M Fujii & DX Hou (2007) Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free Radic Biol Med 42, 16901703.

128 F Hong , ML Freeman & DC Liebler (2005) Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane. Chem Res Toxicol 18, 19171926.

129 F Hong , KR Sekhar , ML Freeman & DC Liebler (2005) Specific patterns of electrophile adduction trigger Keap1 ubiquitination and Nrf2 activation. J Biol Chem 280, 3176831775.

130 N Wakabayashi , AT Dinkova-Kostova , WD Holtzclaw , MI Kang , A Kobayashi , M Yamamoto , TW Kensler & P Talalay (2004) Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers. Proc Natl Acad Sci U S A 101, 20402045.

131 AL Eggler , G Liu , JM Pezzuto , RB van Breemen & AD Mesecar (2005) Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2. Proc Natl Acad Sci U S A 102, 1007010075.

132 SB Le , MK Hailer , S Buhrow , Q Wang , K Flatten , P Pediaditakis , KC Bible , LD Lewis , EA Sausville , YP Pang , MM Ames , JJ Lemasters , EL Holmuhamedov & SH Kaufmann (2007) Inhibition of mitochondrial respiration as a source of adaphostin-induced reactive oxygen species and cytotoxicity. J Biol Chem aufmann 282, 88608872.

133 A Wiseman (2006) Oxygen-induced reperfusion-injury is caused by ROS: amelioration is possible by recombinant-DNA antioxidant enzymes and mimics in selected tissues. Med Hypotheses 66, 329331.

134 DN Criddle , S Gillies , HK Baumgartner-Wilson , M Jaffar , EC Chinje , S Passmore , M Chvanov , S Barrow , OV Gerasimenko , AV Tepikin , R Sutton & OH Petersen (2006) Menadione-induced reactive oxygen species generation via redox cycling promotes apoptosis of murine pancreatic acinar cells. J Biol Chem 281, 4048540492.

135 S McCarthy , M Somayajulu , M Sikorska , H Borowy-Borowski & S Pandey (2004) Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble coenzyme Q10. Toxicol Appl Pharmacol 201, 2131.

136 P Srinivas , G Gopinath , A Banerji , A Dinakar & G Srinivas (2004) Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells. Mol Carcinog 40, 201211.

137 BJ Phillips , D Anderson & SD Gangolli (1986) Influence of phagocyte-derived active oxygen species in tissue responses to tumour promoters and irritants. Food Chem Toxicol 24, 681683.

138 Y Minamiyama , S Takemura , S Hai , S Suehiro & S Okada (2006) Vitamin E deficiency accelerates nitrate tolerance via a decrease in cardiac P450 expression and increased oxidative stress. Free Radic Biol Med 40, 808816.

139 H Isomura , K Fujie , K Shibata , N Inoue , T Iizuka , G Takebe , K Takahashi , J Nishihira , H Izumi & W Sakamoto (2004) Bone metabolism and oxidative stress in postmenopausal rats with iron overload. Toxicology 197, 93100.

140 P Gregorevic , GS Lynch & DA Williams (2001) Hyperbaric oxygen modulates antioxidant enzyme activity in rat skeletal muscles. Eur J Appl Physiol 86, 2427.

141 SX He , JY Luo , YP Wang , YL Wang , H Fu , JL Xu , G Zhao & EQ Liu (2006) Effects of extract from Ginkgo biloba on carbon tetrachloride-induced liver injury in rats. World J Gastroenterol 12, 39243928.

142 R Bruck , M Ashkenazi , S Weiss , I Goldiner , H Shapiro , H Aeed , O Genina , Z Helpern & M Pines (2007) Prevention of liver cirrhosis in rats by curcumin. Liver Int 27, 373383.

143 S Wirtz , C Neufert , B Weigmann & MF Neurath (2007) Chemically induced mouse models of intestinal inflammation. Nat Protoc 2, 541546.

144 K Fujimoto , S Arakawa , Y Shibaya , H Miida , Y Ando , H Yasumo , A Hara , M Uchiyama , H Iwabuchi , W Takasaki , S Manabe & T Yamoto (2006) Characterization of phenotypes in Gstm1-null mice by cytosolic and in vivo metabolic studies using 1,2-dichloro-4-nitrobenzene. Drug Metab Dispos 34, 14951501.

145 L Erker , R Schubert , S Elchuri , TT Huang , D Tarin , K Mueller , S Zielen , CJ Epstein & A Wynshaw-Boris (2006) Effect of the reduction of superoxide dismutase 1 and 2 or treatment with alpha-tocopherol on tumorigenesis in Atm-deficient mice. Free Radic Biol Med 41, 590600.

147 N Hamaue , A Ogata , M Terado , K Ohno , S Kikuchi , H Sasaki , K Tashiro , M Hirafuji & M Minami (2006) Brain catecholamine alterations and pathological features with aging in Parkinson disease model rat induced by Japanese encephalitis virus. Neurochem Res 31, 14511455.

148 Y Zha , VT Le , Y Higami , I Shimokawa , T Taguchi & MS Razzaque (2006) Life-long suppression of growth hormone-insulin-like growth factor I activity in genetically altered rats could prevent age-related renal damage. Endocrinology 147, 56905698.

149 E Larsen , K Kwon , F Coin , JM Egly & A Klungland (2004) Transcription activities at 8-oxoG lesions in DNA. DNA Repair (Amst) 3, 14571468.

150 Y Xie , H Yang , C Cunanan , K Okamoto , D Shibata , J Pan , DE Barnes , T Lindahl , M McIlhatton , R Fishel & JH Miller (2004) Deficiencies in mouse Myh and Ogg1 result in tumor predisposition and G to T mutations in codon 12 of the K-ras oncogene in lung tumors. Cancer Res 64, 30963102.

151 PP Glasziou & SL Sanders (2002) Investigating causes of heterogeneity in systematic reviews. Stat Med 21, 15031511.

152 A Hartmann , AM Niess , M Grunert-Fuchs , B Poch & G Speit (1995) Vitamin E prevents exercise-induced DNA damage. Mutat Res 346, 195202.

153 JM Sacheck , PE Milbury , JG Cannon , R Roubenoff & JB Blumberg (2003) Effect of vitamin E and eccentric exercise on selected biomarkers of oxidative stress in young and elderly men. Free Radic Biol Med 34, 15751588.

154 C Dennog , P Radermacher , YA Barnett & G Speit (1999) Antioxidant status in humans after exposure to hyperbaric oxygen. Mutat Res 428, 8389.

155 S Astley , A Langrish-Smith , S Southon & M Sampson (1999) Vitamin E supplementation and oxidative damage to DNA and plasma LDL in type 1 diabetes. Diabetes Care 22, 16261631.

156 ME Lean , M Noroozi , I Kelly , J Burns , D Talwar , N Sattar & A Crozier (1999) Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes 48, 176181.

157 MJ Sampson , S Astley , T Richardson , G Willis , IR Davies , DA Hughes & S Southon (2001) Increased DNA oxidative susceptibility without increased plasma LDL oxidizability in Type II diabetes: effects of alpha-tocopherol supplementation. Clin Sci (Lond) 101, 235241.

158 P Jaruga , B Jaruga , D Gackowski , A Olczak , W Halota , M Pawlowska & R Olinski (2002) Supplementation with antioxidant vitamins prevents oxidative modification of DNA in lymphocytes of HIV-infected patients. Free Radic Biol Med 32, 414420.

159 M Soccio , E Toniato , V Evangelista , M Carluccio & R De Caterina (2005) Oxidative stress and cardiovascular risk: the role of vascular NAD(P)H oxidase and its genetic variants. Eur J Clin Invest 35, 305314.

160 S Hercberg , S Czernichow & P Galan (2006) Antioxidant vitamins and minerals in prevention of cancers: lessons from the SU.VI.MAX study. Br J Nutr 96, Suppl. 1, S28S30.

162 E Kan , U Undeger , M Bali & N Basaran (2002) Assessment of DNA strand breakage by the alkaline COMET assay in dialysis patients and the role of vitamin E supplementation. Mutat Res 520, 151159.

163 MD Evans , MS Cooke , M Akil , A Samanta & J Lunec (2000) Aberrant processing of oxidative DNA damage in systemic lupus erythematosus. Biochem Biophys Res Commun 273, 894898.

164 LJ Berliner , V Khramtsov , H Fujii & TL Clanton (2001) Unique in vivo applications of spin traps. Free Radic Biol Med 30, 489499.

165 N Khan , CM Wilmot , GM Rosen , E Demidenko , J Sun , J Joseph , J O'Hara , B Kalyanaraman & HM Swartz (2003) Spin traps: in vitro toxicity and stability of radical adducts. Free Radic Biol Med 34, 14731481.

166 SE Bottle , GR Hanson & AS Micallef (2003) Application of the new EPR spin trap 1,1,3-trimethylisoindole N-oxide (TMINO) in trapping HO. and related biologically important radicals. Org Biomol Chem 1, 25852589.

167 H Karoui , J-L Clément , A Rockenbauer , D Siri & P Tordo (2004) Synthesis and structure of 5,5-diethoxycarbonyl-1-pyrroline N-oxide (DECPO). Application to superoxide radical trapping. Tetrahedron Lett 45, 149152.

168 K Stolze , N Udilova , T Rosenau , A Hofinger & H Nohl (2003) Spin trapping of superoxide, alkyl- and lipid-derived radicals with derivatives of the spin trap EPPN. Biochem Pharmacol 66, 17171726.

169 H Zhao , J Joseph , H Zhang , H Karoui & B Kalyanaraman (2001) Synthesis and biochemical applications of a solid cyclic nitrone spin trap: a relatively superior trap for detecting superoxide anions and glutathiyl radicals. Free Radic Biol Med 31, 599606.

170 B Halliwell & M Whiteman (2004) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 142, 231255.

172 A Ghiselli , M Serafini , G Maiani , E Azzini & A Ferro-Luzzi (1995) A fluorescence-based method for measuring total plasma antioxidant capability. Free Radic Biol Med 18, 2936.

173 AN Glazer (1990) Phycoerythrin fluorescence-based assay for reactive oxygen species. Methods Enzymol 186, 161168.

174 G Cao , HM Alessio & RG Cutler (1993) Oxygen-radical absorbance capacity assay for antioxidants. Free Radic Biol Med 14, 303311.

175 RL Prior , X Wu & K Schaich (2005) Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements. J Agric Food Chem 53, 42904302.

176 D Huang , B Ou , M Hampsch-Woodill , JA Flanagan & EK Deemer (2002) Development and validation of oxygen radical absorbance capacity assay for lipophilic antioxidants using randomly methylated β-cyclodextrin as the solubility enhancer. J Agric Food Chem 50, 18151821.

177 D Huang , B Ou , M Hampsch-Woodill , JA Flanagan & RL Prior (2002) High-throughput assay of oxygen radical absorbance capacity (ORAC) using a multichannel liquid handling system coupled with a microplate fluorescence reader in 96-well format. J Agric Food Chem 50, 44374444.

178 S Lussignoli , M Fraccaroli , G Andrioli , G Brocco & P Bellavite (1999) A microplate-based colorimetric assay of the total peroxyl radical trapping capability of human plasma. Anal Biochem 269, 3844.

179 EN Frankel & AS Meyer (2000) The problems of using one-dimensional methods to evaluate multifunctional food and biological antioxidants. J Sci Food Agric 80, 19251941.

180 DDM Wayner , GW Burton , KU Ingold & S Locke (1985) Quantitative measurement of the total, peroxyl radical-trapping antioxidant capability of human blood plasma by controlled peroxidation. The important contribution made by plasma proteins. FEBS Lett 187, 3337.

181 RJ DeLange & AN Glazer (1989) Phycoerythrin fluorescence-based assay for peroxy radicals: a screen for biologically relevant protective agents. Anal Biochem 177, 300306.

183 C Rota , CF Chignell & RP Mason (1999) Evidence for free radical formation during the oxidation of 2′-7′-dichlorofluorescin to the fluorescent dye 2′-7′-dichlorofluorescein by horseradish peroxidase: possible implications for oxidative stress measurements. Free Radic Biol Med 27, 873881.

184 A Ghiselli , M Serafini , F Natella & C Scaccini (2000) Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free Radic Biol Med 29, 11061114.

185 GW Winston , F Regoli , AJ Dugas Jr, JH Fong & KA Blanchard (1998) A rapid gas chromatographic assay for determining oxyradical scavenging capacity of antioxidants and biological fluids. Free Radic Biol Med 24, 480493.

186 F Regoli & GW Winston (1999) Quantification of total oxidant scavenging capacity of antioxidants for peroxynitrite, peroxyl radicals, and hydroxyl radicals. Toxicol Appl Pharmacol 156, 96105.

187 R Lichtenthaler & F Marx (2005) Total oxidant scavenging capacities of common European fruit and vegetable juices. J Agric Food Chem 53, 103110.

188 H Lundqvist , LJ Kricka , RA Stott , GH Thorpe & C Dahlgren (1995) Influence of different luminols on the characteristics of the chemiluminescence reaction in human neutrophils. J Biolumin Chemilumin 10, 353359.

189 TP Whitehead , GHG Thorpe & SRJ Maxwell (1992) Enhanced chemiluminescent assay for antioxidant capacity in biological fluids. Analytica Chimica Acta 266, 265277.

190 V Witko-Sarsat , AT Nguyen , J Knight & B Descamps-Latscha (1992) Pholasin®: a new chemiluminescent probe for the detection of chloramines derived from human phagocytes. Free Radic Biol Med 13, 8388.

192 J Glebska & WH Koppenol (2005) Chemiluminescence of Pholasin caused by peroxynitrite. Free Radic Biol Med 38, 10141022.

193 I Popov , H Völker & G Lewin (2001) Photochemiluminescent detection of antiradical activity. V. Application in combination with the hydrogen peroxide-initiated chemiluminescence of blood plasma proteins to evaluate antioxidant homeostasis in humans. Redox Report 6, 4348.

196 C Rice-Evans , D Leake , R Bruckdorfer & AT Diplock (1996) Practical approaches to low density lipoprotein oxidation: whys, wherefores and pitfalls. Free Radic Res 25, 285311.

197 K-H Wagner , R Tomasch & I Elmadfa (2001) Impact of diets containing corn oil or olive/sunflower oil mixture on the human plasma and lipoprotein lipid metabolism. Eur J Nutr 40, 161167.

199 EN Frankel , JB German & PA Davis (1992) Headspace gas chromatography to determine human low density lipoprotein oxidation. Lipids 27, 10471051.

200 W Bors , C Michel & M Saran (1984) Inhibition of the bleaching of the carotenoid crocin. A rapid test for quantifying antioxidant activity. Biochim Biophys Acta 796, 312319.

201 F Tubaro , A Ghiselli , P Rapuzzi , M Maiorino & F Ursini (1998) Analysis of plasma antioxidant capacity by competition kinetics. Free Radic Biol Med 24, 12281234.

202 NJ Miller , C Rice-Evans , MJ Davies , V Gopinathan & A Milner (1993) A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci 84, 407412.

203 R Re , N Pellegrini , A Proteggente , A Pannala , M Yang & C Rice-Evans (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 26, 12311237.

204 R Van Den Berg , G Haenen , H Van Den Berg & A Bast (1999) Applicability of an improved Trolox equivalent antioxidant capacity (TEAC) assay for evaluation of antioxidant capacity measurements of mixtures. Food Chem 66, 511517.

205 NJ Miller , J Sampson , LP Candeias , PM Bramley & CA Rice-Evans (1996) Antioxidant activities of carotenes and xanthophylls. FEBS Lett 384, 240242.

206 IFF Benzie & JJ Strain (1996) The ferric reducing ability of plasma (FRAP) as a measure of ‘antioxidant power’: the FRAP assay. Anal Biochem 239, 7076.

207 IFF Benzie & YT Szeto (1999) Total antioxidant capacity of teas by the ferric reducing/antioxidant power assay. J Agric Food Chem 47, 633636.

208 B Ou , D Huang , M Hampsch-Woodill , JA Flanagan & EK Deemer (2002) Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: a comparative study. J Agric Food Chem 50, 31223128.

209 R Pulido , L Bravo & F Saura-Calixto (2000) Antioxidant activity of dietary polyphenols as determined by a modified ferric reducing/antioxidant power assay. J Agric Food Chem 48, 33963402.

210 R Apak , K Guclu , M Ozyurek & SE Karademir (2004) Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. J Agric Food Chem 52, 79707981.

211 W Brand-Williams , ME Cuvelier & C Berset (1995) Use of a free radical method to evaluate antioxidant activity. Lebensm Wiss Technol 28, 2530.

214 D Huang , B Ou & RL Prior (2005) The chemistry behind antioxidant capacity assays. J Agric Food Chem 53, 18411856.

215 G Spiteller (2006) Peroxyl radicals: inductors of neurodegenerative and other inflammatory diseases. Their origin and how they transform cholesterol, phospholipids, plasmalogens, polyunsaturated fatty acids, sugars, and proteins into deleterious products. Free Radic Biol Med 41, 362387.

216 K Yagi (1976) A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med 15, 212216.

217 JM Gutteridge (1986) Aspects to consider when detecting and measuring lipid peroxidation. Free Radic Res Commun 1, 173184.

218 EA Meagher & GA Fitzgerald (2000) Indices of lipid peroxidation in vivo: strengths and limitations. Free Radic Biol Med 28, 17451750.

220 F Karatas , M Karatepe & A Baysar (2002) Determination of free malondialdehyde in human serum by high-performance liquid chroma tography. Anal Biochem 311, 7679.

222 AS Sim , C Salonikas , D Naidoo & DEL Wilcken (2003) Improved method for plasma malondialdehyde measurement by high-performance liquid chromatography using methyl malondialdehyde as an internal standard. J Chromatogr B Analyt Technol Biomed Life Sci 785, 337344.

223 J-P Steghens , AL Van Kappel , I Denis & C Collombel (2001) Diaminonaphtalene, a new highly specific regent for HPLC–UV measurement of total and free malondialdehyde in human plasma or serum. Free Radic Biol Med 31, 242249.

225 CD Stalikas & CN Konidari (2001) Analysis of malondialdehyde in biological matrices by capillary gas chromatography with electron-capture detection and mass spectrometry. Anal Biochem 290, 108115.

226 D Del Rio , AJ Stewart & N Pellegrini (2005) A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 15, 316328.

227 A Ramel , K-H Wagner & I Elmadfa (2004) Plasma antioxidants and lipid oxidation after submaximal resistance exercise in men. Eur J Nutr 43, 26.

229 JD Morrow , KE Hill , RF Burk , TM Nammour , KF Badr & LJ Roberts II (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A 87, 93839387.

230 GL Milne , ES Musiek & JD Morrow (2005) F2-isoprostanes as markers of oxidative stress in vivo: an overview. Biomarkers 10, Suppl. 1, S10S23.

231 LJ Roberts II & JD Morrow (2000) Measurement of F2-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med 28, 505513.

232 IS Young (2005) Oxidative stress and vascular disease: insights from isoprostane measurement. Clin Chem 51, 1415.

233 E Schwedhelm & RH Boger (2003) Application of gas chromatography–mass spectrometry for analysis of isoprostanes: their role in cardiovascular disease. Clin Chem Lab Med 41, 15521561.

234 H Frank , T Hintze , D Bimboes & H Remmer (1980) Monitoring lipid peroxidation by breath analysis: endogenous hydrocarbons and their metabolic elimination. Toxicol Appl Pharmacol 56, 337344.

235 FJ Romero , F Bosch-Morell , MJ Romero , EJ Jareno , B Romero , N Marin & J Roma (1998) Lipid peroxidation products and antioxidants in human disease. Environ Health Perspect 106, Suppl. 5, 12291234.

236 TH Risby & SS Sehnert (1999) Clinical application of breath biomarkers of oxidative stress status. Free Radic Biol Med 27, 11821192.

237 H Esterbauer , RJ Schaur & H Zollner (1991) Chemistry and Biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11, 81128.

238 A Benedetti , M Comporti & H Esterbauer (1980) Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids. Biochim Biophys Acta 620, 281296.

239 GM Cahuana , JR Tejedo , J Jimenez , R Ramirez , F Sobrino & FJ Bedoya (2003) Involvement of advanced lipooxidation end products (ALEs) and protein oxidation in the apoptotic actions of nitric oxide in insulin secreting RINm5F cells. Biochem Pharmacol 66, 19631971.

240 AE Holley , MK Walker , KH Cheeseman & TF Slater (1993) Measurement of n-alkanals and hydroxyalkenals in biological samples. Free Radic Biol Med 15, 281289.

241 R Sharma , D Brown , S Awasthi , Y Yang , A Sharma , B Patrick , MK Saini , SP Singh , P Zimniak , SV Singh & YC Awasthi (2004) Transfection with 4-hydroxynonenal-metabolizing glutathione S-transferase isozymes leads to phenotypic transformation and immortalization of adherent cells. Eur J Biochem 271, 16901701.

242 R Agarwal (2004) Chronic kidney disease is associated with oxidative stress independent of hypertension. Clin Nephrol 61, 377383.

243 CC Winterbourn & IH Buss (1999) Protein carbonyl measurement by enzyme-linked immunosorbent assay. Methods Enzymol 300, 106111.

245 RL Levine , D Garland , CN Oliver , A Amici , I Climent , A-G Lenz , B-W Ahn , S Shaltiel & ER Stadtman (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186, 464478.

246 DH Alamdari , E Kostidou , K Paletas , M Sarigianni , AGP Konstas , A Karapiperidou & G Koliakos (2005) High sensitivity enzyme-linked immunosorbent assay (ELISA) method for measuring protein carbonyl in samples with low amounts of protein. Free Radic Biol Med 39, 13621367.

247 V Witko-Sarsat , M Friedlander , C Capeillere-Blandin , T Nguyen-Khoa , AT Nguyen , J Zingraff , P Jungers & B Descamps-Latscha (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 49, 13041313.

248 C Capeillere-Blandin , V Gausson , B Descamps-Latscha & V Witko-Sarsat (2004) Biochemical and spectrophotometric significance of advanced oxidized protein products. Biochim Biophys Acta 1689, 91102.

250 H Kaneda , J Taguchi , K Ogasawara , T Aizawa & M Ohno (2002) Increased level of advanced oxidation protein products in patients with coronary artery disease. Atherosclerosis 162, 221225.

251 M Kalousova , T Zima , V Tesar , S Dusilova-Sulkova & J Skrha (2005) Advanced glycoxidation end products in chronic diseases – clinical chemistry and genetic background. Mutat Res 579, 3746.

255 S Knasmüller , H Steinkellner , BJ Majer , EC Nobis , G Scharf & F Kassie (2002) Search for dietary antimutagens and anticarcinogens: methodological aspects and extrapolation problems. Food Chem Toxicol 40, 10511062.

256 S Knasmüller , BJ Majer & C Buchmann (2004) Identifying antimutagenic constituents of food. In Functional Foods, Ageing and Degenerative Disease, pp. 581614 [ C Remacle and B Reusens , editors]. Cambridge, England/Boca Raton, Boston, New York, Washington, DC: CRC Press.

259 BN Ames (1972) A bacterial system for detecting mutagens and carcinogens. In Mutagenic Effects of Environmental Contaminants, pp. 5766 [ HE Sutton and MI Harris , editors]. New York: Academic Press.

260 DE Levin , M Hollstein , MF Christman , EA Schwiers & BN Ames (1982) A new Salmonella tester strain (TA102) with A X T base pairs at the site of mutation detects oxidative mutagens. Proc Natl Acad Sci U S A 79, 74457449.

262 B Rutten & E Gocke (1988) The ‘antimutagenic’ effect of cinnamaldehyde is due to a transient growth inhibition. Mutat Res 201, 97105.

263 FE Wurgler , U Friederich , E Furer & M Ganss (1990) Salmonella/mammalian microsome assay with tetranitromethane and 3-nitro-l-tyrosine. Mutat Res 244, 714.

264 O Ostling & KJ Johanson (1984) Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem Biophys Res Commun 123, 291298.

265 RR Tice , E Agurell , D Anderson , B Burlinson , A Hartmann , H Kobayashi , Y Miyamae , E Rojas , JC Ryu & YF Sasaki (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35, 206221.

266 NP Singh , MT McCoy , RR Tice & EL Schneider (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175, 184191.

267 YF Sasaki , K Sekihashi , F Izumiyama , E Nishidate , A Saga , K Ishida & S Tsuda (2000) The comet assay with multiple mouse organs: comparison of comet assay results and carcinogenicity with 208 chemicals selected from the IARC monographs and U.S. NTP Carcinogenicity Database. Crit Rev Toxicol 30, 629799.

268 VS Dhillon , P Thomas & M Fenech (2004) Comparison of DNA damage and repair following radiation challenge in buccal cells and lymphocytes using single-cell gel electrophoresis. Int J Radiat Biol 80, 517528.