Plant flavonoids in cancer chemoprevention: role in genome stability

The Journal of Nutritional Biochemistry - Tập 45 - Trang 1-14 - 2017
Vazhappilly Cijo George1, Graham Dellaire2, H.P. Vasantha Rupasinghe1,2
1Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, Nova Scotia, Canada
2Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada

Tài liệu tham khảo

Seyfried, 2010, Cancer as a metabolic disease, Nutr Metab (Lond), 7, 10.1186/1743-7075-7-7 Trosko, 2012, Evolution of energy metabolism, stem cells and cancer stem cells: how the Warburg and Barker hypotheses might be linked, Int J Stem Cells, 5, 39, 10.15283/ijsc.2012.5.1.39 Block, 2015, Designing a broad-spectrum integrative approach for cancer prevention and treatment, Semin Cancer Biol, S276, 10.1016/j.semcancer.2015.09.007 Wajed, 2001, DNA methylation: an alternative pathway to cancer, Ann Surg, 234, 10, 10.1097/00000658-200107000-00003 Weitzman, 2010, Genomes in conflict: maintaining genome integrity during virus infection, Annu Rev Microbiol, 64, 61, 10.1146/annurev.micro.112408.134016 B, 2008, Destabilization of the cancer genome Rajendran, 2011, Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells, Clin Epigenetics, 3, 4, 10.1186/1868-7083-3-4 Cheung-Ong, 2013, DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology, Chem Biol, 20, 648, 10.1016/j.chembiol.2013.04.007 Woods, 2013, Chemotherapy induced DNA damage response: convergence of drugs and pathways, Cancer Biol Ther, 14, 379, 10.4161/cbt.23761 Helleday, 2008, DNA repair pathways as targets for cancer therapy, Nat Rev Cancer, 8, 193, 10.1038/nrc2342 Kelland, 2007, The resurgence of platinum-based cancer chemotherapy, Nat Rev Cancer, 7, 573, 10.1038/nrc2167 Longley, 2003, 5-Fluorouracil: mechanisms of action and clinical strategies, Nat Rev Cancer, 3, 330, 10.1038/nrc1074 Pommier, 2006, Topoisomerase I inhibitors: camptothecins and beyond, Nat Rev Cancer, 6, 789, 10.1038/nrc1977 Zhou, 2000, The DNA damage response: putting checkpoints in perspective, Nature, 408, 433, 10.1038/35044005 Ciccia, 2010, The DNA damage response: making it safe to play with knives, Mol Cell, 40, 179, 10.1016/j.molcel.2010.09.019 Bartkova, 2005, DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis, Nature, 434, 864, 10.1038/nature03482 Pandita, 2009, Chromatin remodeling finds its place in the DNA double-strand break response, Nucleic Acids Res, 37, 1363, 10.1093/nar/gkn1071 Stokes, 2007, Profiling of UV-induced ATM/ATR signaling pathways, Proc Natl Acad Sci U S A, 104, 19855, 10.1073/pnas.0707579104 Jette, 2015, The DNA-dependent protein kinase: a multifunctional protein kinase with roles in DNA double strand break repair and mitosis, Prog Biophys Mol Biol, 117, 194, 10.1016/j.pbiomolbio.2014.12.003 Matsuoka, 2007, ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage, Science, 316, 1160, 10.1126/science.1140321 Gong, 2013, Mammalian DNA repair: HATs and HDACs make their mark through histone acetylation, Mutat Res-Fund Mol M, 750, 23, 10.1016/j.mrfmmm.2013.07.002 Barneda-Zahonero, 2012, Histone deacetylases and cancer, Mol Oncol, 6, 579, 10.1016/j.molonc.2012.07.003 Kachhap, 2010, Downregulation of homologous recombination DNA repair genes by HDAC inhibition in prostate cancer is mediated through the E2F1 transcription factor, PLoS One, 5, 10.1371/journal.pone.0011208 Bonisch, 2012, Histone H2A variants in nucleosomes and chromatin: more or less stable?, Nucleic Acids Res, 40, 10719, 10.1093/nar/gks865 Harper, 2007, The DNA damage response: ten years after, Mol Cell, 28, 739, 10.1016/j.molcel.2007.11.015 Petrini, 2007, Cell signaling. A touching response to damage, Science, 316, 1138, 10.1126/science.1143700 Zannini, 2014, CHK2 kinase in the DNA damage response and beyond, J Mol Cell Biol, 6, 442, 10.1093/jmcb/mju045 Bhattacharyya, 2000, The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin, J Biol Chem, 275, 23899, 10.1074/jbc.C000276200 Dray, 2010, Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2, Nat Struct Mol Biol, 17, 1255, 10.1038/nsmb.1916 Buisson, 2010, Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination, Nat Struct Mol Biol, 17, 1247, 10.1038/nsmb.1915 Meek, 2004, The p53 response to DNA damage, DNA Repair (Amst), 3, 1049, 10.1016/j.dnarep.2004.03.027 Nevanlinna, 2006, The CHEK2 gene and inherited breast cancer susceptibility, Oncogene, 25, 5912, 10.1038/sj.onc.1209877 Solomon, 2012, Inherited pancreatic cancer syndromes, Cancer J, 18, 485, 10.1097/PPO.0b013e318278c4a6 McBride, 2014, Li-Fraumeni syndrome: cancer risk assessment and clinical management, Nat Rev Clin Oncol, 11, 260, 10.1038/nrclinonc.2014.41 O'Sullivan, 2014, Beyond breast and ovarian cancers: PARP inhibitors for BRCA mutation-associated and BRCA-like solid tumors, Front Oncol, 4, 42 Langie, 2015, Causes of genome instability: the effect of low dose chemical exposures in modern society, Carcinogenesis, 36, S61, 10.1093/carcin/bgv031 Ayoub, 2009, The carboxyl terminus of Brca2 links the disassembly of Rad51 complexes to mitotic entry, Curr Biol, 19, 1075, 10.1016/j.cub.2009.05.057 Chen, 2008, Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair, Cell, 134, 231, 10.1016/j.cell.2008.06.035 Bishop, 2015, The interaction between epigenetics, nutrition and the development of cancer, Nutrients, 7, 922, 10.3390/nu7020922 Shukla, 2014, Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention, Cancer Lett, 355, 9, 10.1016/j.canlet.2014.09.017 Berman, 2012, Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains, Nat Genet, 44, 40, 10.1038/ng.969 Lahtz, 2011, Epigenetic changes of DNA repair genes in cancer, J Mol Cell Biol, 3, 51, 10.1093/jmcb/mjq053 Jiricny, 2006, The multifaceted mismatch-repair system, Nat Rev Mol Cell Biol, 7, 335, 10.1038/nrm1907 Hoeijmakers, 2009, DNA damage, aging, and cancer. (vol 361, p 1475, 2009), N Engl J Med, 361, 1914 Bennardo, 2008, Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair, PLoS Genet, 4, 10.1371/journal.pgen.1000110 Svetlova, 2009, Application of new methods for detection of DNA damage and repair, Int Rev Cel Mol Biol, 277, 217, 10.1016/S1937-6448(09)77006-6 Collins, 2001, Inter-individual differences in repair of DNA base oxidation, measured in vitro with the comet assay, Mutagenesis, 16, 297, 10.1093/mutage/16.4.297 Collins, 2009, Investigating oxidative DNA damage and its repair using the comet assay, Mutat Res, 681, 24, 10.1016/j.mrrev.2007.10.002 Charles, 2012, Measurement of the influence of flavonoids on DNA repair kinetics using the comet assay, Food Chem, 135, 2974, 10.1016/j.foodchem.2012.06.112 Schmid, 2012, Differences in phosphorylated histone H2AX foci formation and removal of cells exposed to low and high linear energy transfer radiation, Curr Genomics, 13, 418, 10.2174/138920212802510501 Mailand, 2007, RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins, Cell, 131, 887, 10.1016/j.cell.2007.09.040 Hilchie, 2011, Pleurocidin-family cationic antimicrobial peptides are cytolytic for breast carcinoma cells and prevent growth of tumor xenografts, Breast Cancer Res, 13, 10.1186/bcr3043 Chaurio, 2014, The progression of cell death affects the rejection of allogeneic tumors in immune-competent mice - implications for cancer therapy, Front Immunol, 5, 560, 10.3389/fimmu.2014.00560 Gescher, 1998, Suppression of tumour development by substances derived from the diet-mechanisms and clinical implications, Br J Clin Pharmacol, 45, 1, 10.1046/j.1365-2125.1998.00640.x De Angelis, 2008, Side effects related to systemic cancer treatment: are we changing the promethean experience with molecularly targeted therapies?, Curr Oncol, 15, 198, 10.3747/co.v15i4.362 Chou, 2010, Drug combination studies and their synergy quantification using the Chou-Talalay method, Cancer Res, 70, 440, 10.1158/0008-5472.CAN-09-1947 Chabner, 2005, Timeline: chemotherapy and the war on cancer, Nat Rev Cancer, 5, 65, 10.1038/nrc1529 Monasterio, 2004, Flavonoids induce apoptosis in human leukemia U937 cells through caspase- and caspase-calpain-dependent pathways, Nutr Cancer, 50, 90, 10.1207/s15327914nc5001_12 Brusselmans, 2005, Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity, J Biol Chem, 280, 5636, 10.1074/jbc.M408177200 Hussain, 2012, Current approaches toward production of secondary plant metabolites, J Pharm Bioallied Sci, 4, 10, 10.4103/0975-7406.92725 Fernando, 2013, Anticancer properties of phytochemicals present in medicinal plants of North America Ziaullah, 2015, Application of NMR spectroscopy in plant phenolics associated with human health Jones, 2012, Target-based selection of flavonoids for neurodegenerative disorders, Trends Pharmacol Sci, 33, 602, 10.1016/j.tips.2012.08.002 Thilakarathna, 2013, Flavonoid bioavailability and attempts for bioavailability enhancement, Nutrients, 5, 3367, 10.3390/nu5093367 Chow, 2011, Pharmacokinetic and chemoprevention studies on tea in humans, Pharmacol Res, 64, 105 Marin, 2015, Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties, Biomed Res Int, 2015, 905215, 10.1155/2015/905215 Landete, 2012, Updated knowledge about polyphenols: functions, bioavailability, metabolism, and health, Crit Rev Food Sci Nutr, 52, 936, 10.1080/10408398.2010.513779 Kim, 2015, Gut microbiota-mediated drug-antibiotic interactions, Drug Metab Dispos, 43, 1581, 10.1124/dmd.115.063867 Graefe, 2001, Pharmacokinetics and bioavailability of quercetin glycosides in humans, J Clin Pharmacol, 41, 492, 10.1177/00912700122010366 Manach, 2005, Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies, Am J Clin Nutr, 81, 230S, 10.1093/ajcn/81.1.230S Matsuo, 2005, Cytotoxicity of flavonoids toward cultured normal human cells, Biol Pharm Bull, 28, 253, 10.1248/bpb.28.253 Shanmugam, 2011, Targeting cell signaling and apoptotic pathways by dietary agents: role in the prevention and treatment of cancer, Nutr Cancer, 63, 161, 10.1080/01635581.2011.523502 Rupasinghe, 2014 Arumuggam, 2015, A review: phytochemicals targeting JAK/STAT signaling and IDO expression in cancer, Phytother Res, 29, 805, 10.1002/ptr.5327 Meyer, 2006, Bioavailability of apigenin from apiin-rich parsley in humans, Ann Nutr Metab, 50, 167, 10.1159/000090736 Das, 2013, Apigenin, a bioactive flavonoid from Lycopodium clavatum, stimulates nucleotide excision repair genes to protect skin keratinocytes from ultraviolet B-induced reactive oxygen species and DNA damage, J Acupunct Meridian Stud, 6, 252, 10.1016/j.jams.2013.07.002 Mazza, 1995, Anthocyanins in grapes and grape products, Crit Rev Food Sci Nutr, 35, 341, 10.1080/10408399509527704 Birt, 1997, Inhibition of ultraviolet light induced skin carcinogenesis in SKH-1 mice by apigenin, a plant flavonoid, Anticancer Res, 17, 85 Shi, 2015, Apigenin, a dietary flavonoid, inhibits proliferation of human bladder cancer T-24 cells via blocking cell cycle progression and inducing apoptosis, Cancer Cell Int, 15, 33, 10.1186/s12935-015-0186-0 Gates, 2009, Flavonoid intake and ovarian cancer risk in a population-based case–control study, Int J Cancer, 124, 1918, 10.1002/ijc.24151 Duarte, 2013, Apigenin protects endothelial cells from lipopolysaccharide (LPS)-induced inflammation by decreasing caspase-3 activation and modulating mitochondrial function, Int J Mol Sci, 14, 17664, 10.3390/ijms140917664 Arango, 2012, Apigenin induces DNA damage through the PKCdelta-dependent activation of ATM and H2AX causing down-regulation of genes involved in cell cycle control and DNA repair, Biochem Pharmacol, 84, 1571, 10.1016/j.bcp.2012.09.005 Kroonen, 2012, Casein kinase 2 inhibition modulates the DNA damage response but fails to radiosensitize malignant glioma cells, Int J Oncol, 41, 776, 10.3892/ijo.2012.1489 Yin, 2008, Effects of epigallocatechin-3-gallate on lead-induced oxidative damage, Toxicology, 249, 45, 10.1016/j.tox.2008.04.006 Zhu, 2014, Epigallocatechin-3-gallate (EGCG) protects skin cells from ionizing radiation via heme oxygenase-1 (HO-1) overexpression, J Radiat Res (Tokyo), 55, 1056, 10.1093/jrr/rru047 Morley, 2005, The green tea polyphenol (−)-epigallocatechin gallate and green tea can protect human cellular DNA from ultraviolet and visible radiation-induced damage, Photodermatol Photoimmunol Photomed, 21, 15, 10.1111/j.1600-0781.2005.00119.x Richi, 2012, Radio-modulatory effects of green tea catechin EGCG on pBR322 plasmid DNA and murine splenocytes against gamma-radiation induced damage, Mutat Res, 747, 62, 10.1016/j.mrgentox.2012.04.002 Silva, 2008, Oxidative DNA damage protection and repair by polyphenolic compounds in PC12 cells, Eur J Pharmacol, 601, 50, 10.1016/j.ejphar.2008.10.046 Leung, 2005, Luteolin induced DNA damage leading to human lung squamous carcinoma CH27 cell apoptosis, Eur J Pharmacol, 508, 77, 10.1016/j.ejphar.2004.12.032 Shi, 2007, Luteolin sensitizes the anticancer effect of cisplatin via c-Jun NH2-terminal kinase-mediated p53 phosphorylation and stabilization, Mol Cancer Ther, 6, 1338, 10.1158/1535-7163.MCT-06-0638 George, 2013, Comparative studies to evaluate relative in vitro potency of luteolin in inducing cell cycle arrest and apoptosis in HaCaT and A375 cells, Asian Pac J Cancer Prev, 14, 631, 10.7314/APJCP.2013.14.2.631 Byun, 2010, Luteolin inhibits protein kinase C(epsilon) and c-Src activities and UVB-induced skin cancer, Cancer Res, 70, 2415, 10.1158/0008-5472.CAN-09-4093 Seelinger, 2008, Anti-carcinogenic effects of the flavonoid luteolin, Molecules, 13, 2628, 10.3390/molecules13102628 Rao, 2012, Luteolin induces apoptosis in multidrug resistant cancer cells without affecting the drug transporter function: involvement of cell line-specific apoptotic mechanisms, Int J Cancer, 130, 2703, 10.1002/ijc.26308 Sudan, 2014, Quercetin-3-O-glucoside induces human DNA topoisomerase II inhibition, cell cycle arrest and apoptosis in hepatocellular carcinoma cells, Anticancer Res, 34, 1691 Yamashita, 1999, Mechanism of oxidative DNA damage induced by quercetin in the presence of Cu(II), Mutat Res, 425, 107, 10.1016/S0027-5107(99)00029-9 Min, 2009, Quercetin inhibits hydrogen peroxide-induced DNA damage and enhances DNA repair in Caco-2 cells, Food Chem Toxicol, 47, 2716, 10.1016/j.fct.2009.07.033 Ozyurt, 2014, Quercetin protects radiation-induced DNA damage and apoptosis in kidney and bladder tissues of rats, Free Radic Res, 48, 1247, 10.3109/10715762.2014.945925 Yamazaki, 2014, Quercetin-3-O-glucronide inhibits noradrenaline binding to alpha(2)-adrenergic receptor, thus suppressing DNA damage induced by treatment with 4-hydroxyestradiol and noradrenaline in MCF-10A cells, J Steroid Biochem Mol Biol, 143, 122, 10.1016/j.jsbmb.2014.02.014 Sun, 2013, Assessing dose-dependent differences in DNA-damage, p53 response and genotoxicity for quercetin and curcumin, Toxicol In Vitro, 27, 1877, 10.1016/j.tiv.2013.05.015 Manzolli, 2015, Protective effects of the flavonoid chrysin against methylmercury-induced genotoxicity and alterations of antioxidant status, in vivo, Oxid Med Cell Longev, 2015, 602360, 10.1155/2015/602360 Anand, 2012, Protective role of chrysin against oxidative stress in D-galactose-induced aging in an experimental rat model, Geriatr Gerontol Int, 12, 741, 10.1111/j.1447-0594.2012.00843.x T M, 2014, Effects of chrysin on free radicals and enzymatic antioxidants in Nω-nitro-l-arginine methyl ester: induced hypertensive rats, Int J Nutr Pharmacol Neurol Dis, 4, 112, 10.4103/2231-0738.129600 Iovine, 2011, Synergic effect of genistein and daidzein on UVB-induced DNA damage: an effective photoprotective combination, J Biomed Biotechnol, 2011, 692846, 10.1155/2011/692846 Paixao, 2012, Protective role of malvidin-3-glucoside on peroxynitrite-induced damage in endothelial cells by counteracting reactive species formation and apoptotic mitochondrial pathway, Oxid Med Cell Longev, 2012, 428538, 10.1155/2012/428538 Khandelwal, 2014, Protective effects of common anthocyanidins against genotoxic damage induced by chemotherapeutic drugs in mice, Planta Med, 80, 1278, 10.1055/s-0034-1383050 Kara, 2014, Protective effect of hesperetin and naringenin against apoptosis in ischemia/reperfusion-induced retinal injury in rats, ScientificWorldJournal, 2014, 797824, 10.1155/2014/797824 Trivedi, 2011, Cardioprotective effects of hesperetin against doxorubicin-induced oxidative stress and DNA damage in rat, Cardiovasc Toxicol, 11, 215, 10.1007/s12012-011-9114-2 Lapenna, 2009, Cell cycle kinases as therapeutic targets for cancer, Nat Rev Drug Discov, 8, 547, 10.1038/nrd2907 El-Mahdy, 2008, Naringenin protects HaCaT human keratinocytes against UVB-induced apoptosis and enhances the removal of cyclobutane pyrimidine dimers from the genome, Photochem Photobiol, 84, 307, 10.1111/j.1751-1097.2007.00255.x Boligon, 2012, Protective effects of extracts and flavonoids isolated from Scutia buxifolia Reissek against chromosome damage in human lymphocytes exposed to hydrogen peroxide, Molecules, 17, 5757, 10.3390/molecules17055757 Quan, 2015, Gypenosides attenuate cholesterol-induced DNA damage by inhibiting the production of reactive oxygen species in human umbilical vein endothelial cells, Mol Med Rep, 11, 2845, 10.3892/mmr.2014.3095 Srivastava, 2014, Modification of radiation-induced DNA double strand break repair pathways by chemicals extracted from Podophyllum hexandrum: an in vitro study in human blood leukocytes, Environ Mol Mutagen, 55, 436, 10.1002/em.21853 Shah, 2015, Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation, PLoS One, 10, 10.1371/journal.pone.0120554 Rastogi, 2010, Protection against radiation-induced oxidative damage by an ethanolic extract of Nigella sativa L, Int J Radiat Biol, 86, 719, 10.3109/09553002.2010.484480 Cheng, 2013, Protective effect of extract of Crataegus pinnatifida pollen on DNA damage response to oxidative stress, Food Chem Toxicol, 59, 709, 10.1016/j.fct.2013.07.015 Yeh, 2012, Anti-proliferative effect of methanolic extract of Gracilaria tenuistipitata on oral cancer cells involves apoptosis, DNA damage, and oxidative stress, BMC Complement Altern Med, 12, 10.1186/1472-6882-12-142 Lam, 2012, An aqueous extract of Fagonia cretica induces DNA damage, cell cycle arrest and apoptosis in breast cancer cells via FOXO3a and p53 expression, PLoS One, 7, e40152, 10.1371/journal.pone.0040152 Hsieh, 2012, AKT/mTOR as novel targets of polyphenol piceatannol possibly contributing to inhibition of proliferation of cultured prostate cancer cells, ISRN Urol, 8 Speich, 2008, Platelets undergo phosphorylation of Syk at Y525/526 and Y352 in response to pathophysiological shear stress, Am J Physiol, 295, C1045, 10.1152/ajpcell.90644.2007 Lee, 2009, Piceatannol, a natural stilbene from grapes, induces G1 cell cycle arrest in androgen-insensitive DU145 human prostate cancer cells via the inhibition of CDK activity, Cancer Lett, 285, 166, 10.1016/j.canlet.2009.05.011 Shiratake, 2015, Rose myrtle (Rhodomyrtus tomentosa) extract and its component, piceatannol, enhance the activity of DNA polymerase and suppress the inflammatory response elicited by UVB-induced DNA damage in skin cells, Mol Med Rep, 12, 5857, 10.3892/mmr.2015.4156 Syed, 2011, Inhibition of human melanoma cell growth by the dietary flavonoid fisetin is associated with disruption of Wnt/beta-catenin signaling and decreased Mitf levels, J Invest Dermatol, 131, 1291, 10.1038/jid.2011.6 Huang, 2013, Inhibition of PI3K/Akt/mTOR signaling by natural products, Anticancer Agents Med Chem, 13, 967, 10.2174/1871520611313070001 Sun, 2013, Natural products targeting autophagy via the PI3K/Akt/mTOR pathway as anticancer agents, Anticancer Agents Med Chem, 13, 1048, 10.2174/18715206113139990130 George, 2015, Antioxidant, DNA protective efficacy and HPLC analysis of Annona muricata (soursop) extracts, J Food Sci Technol, 52, 2328, 10.1007/s13197-014-1289-7 Muanda, 2011, Phytochemical composition and antioxidant capacity of three Malian medicinal plant parts, Evid Based Complement Alternat Med, 2011, 674320, 10.1093/ecam/nep109 Ahmed, 2014, Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats, Life Sci, 110, 61, 10.1016/j.lfs.2014.06.023 Guo, 2008, Pomegranate juice is potentially better than apple juice in improving antioxidant function in elderly subjects, Nutr Res, 28, 72, 10.1016/j.nutres.2007.12.001 Liu, 2003, Antitumor and immunomodulatory activity of resveratrol on experimentally implanted tumor of H22 in Balb/c mice, World J Gastroenterol, 9, 1474, 10.3748/wjg.v9.i7.1474 Pasciu, 2010, Akt downregulation by flavin oxidase-induced ROS generation mediates dose-dependent endothelial cell damage elicited by natural antioxidants, Toxicol Sci, 114, 101, 10.1093/toxsci/kfp301 Singh, 2011, Resveratrol (3,5,4′-trihydroxystilbene) protects pregnant mother and fetus from the immunotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin, Mol Nutr Food Res, 55, 209, 10.1002/mnfr.201000206 Zafra-Stone, 2007, Berry anthocyanins as novel antioxidants in human health and disease prevention, Mol Nutr Food Res, 51, 675, 10.1002/mnfr.200700002 Giampieri, 2014, Polyphenol-rich strawberry extract protects human dermal fibroblasts against hydrogen peroxide oxidative damage and improves mitochondrial functionality, Molecules, 19, 7798, 10.3390/molecules19067798 Ochmian, 2010, Yield and chemical composition of blue honeysuckle fruit depending on ripening time, Bull UASVM Hort, 67, 138 Rupasinghe, 2015, Anti-inflammatory activity of haskap cultivars is polyphenols-dependent, Biomolecules, 5, 1079, 10.3390/biom5021079 Rupasinghe, 2012, Haskap (Lonicera caerulea): a new berry crop with high antioxidant capacity, Can J Plant Sci, 92, 1311, 10.4141/cjps2012-073 Zhao, 2012, Protective effect of anthocyanin from Lonicera caerulea var. edulis on radiation-induced damage in mice, Int J Mol Sci, 13, 11773, 10.3390/ijms130911773 Rajnochova Svobodova, 2013, Effects of oral administration of Lonicera caerulea berries on UVB-induced damage in SKH-1 mice. A pilot study, Photochem Photobiol Sci, 12, 1830, 10.1039/c3pp50120e Bonarska-Kujawa, 2014, Biophysical mechanism of the protective effect of blue honeysuckle (Lonicera caerulea L. Var. Kamtschatica Sevast.) polyphenols extracts against lipid peroxidation of erythrocyte and lipid membranes, J Membr Biol, 247, 611, 10.1007/s00232-014-9677-5 Collins, 2013, Kiwifruit as a modulator of DNA damage and DNA repair, Adv Food Nutr Res, 68, 283, 10.1016/B978-0-12-394294-4.00016-X Kang, 2004, Green vegetable drink consumption protects peripheral lymphocytes DNA damage in Korean smokers, Biofactors, 22, 245, 10.1002/biof.5520220149 Pi-Yu, 2013, Indigenous purple vegetable extracts protect against hydrogen peroxide-induced DNA damage in human lymphocytes, Food Nutr Sci, 4, 62, 10.4236/fns.2013.48A008 Calabrese, 2008, Converging concepts: adaptive response, preconditioning, and the Yerkes-Dodson law are manifestations of hormesis, Ageing Res Rev, 7, 8, 10.1016/j.arr.2007.07.001 Calabrese, 2010, Resveratrol commonly displays hormesis: occurrence and biomedical significance, Hum Exp Toxicol, 29, 980, 10.1177/0960327110383625 Mukherjee, 2010, Dose-dependency of resveratrol in providing health benefits, Dose Response, 8, 478, 10.2203/dose-response.09-015.Mukherjee Wang, 1997, Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells, Nutr Cancer, 28, 236, 10.1080/01635589709514582 Vargas, 2010, Hormesis and synergy: pathways and mechanisms of quercetin in cancer prevention and management, Nutr Rev, 68, 418, 10.1111/j.1753-4887.2010.00301.x Kalyuzhny, 2011, Combination of TUNEL assay with immunohistochemistry for simultaneous detection of DNA fragmentation and oxidative cell damage, Methods Mol Biol, 682, 15, 10.1007/978-1-60327-409-8_2 Muslimovic, 2008, An optimized method for measurement of gamma-H2AX in blood mononuclear and cultured cells, Nat Protoc, 3, 1187, 10.1038/nprot.2008.93 Zhao, 2008, Protective effect of hyaluronate on oxidative DNA damage in WI-38 and A549 cells, Int J Oncol, 32, 1159 Chen, 2013, Suppression of DNA-damage checkpoint signaling by Rsk-mediated phosphorylation of Mre11, Proc Natl Acad Sci U S A, 110, 20605, 10.1073/pnas.1306328110 Bombarde, 2010, TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends, EMBO J, 29, 1573, 10.1038/emboj.2010.49 Liu, 2012, Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress, Nucleic Acids Res, 40, 10780, 10.1093/nar/gks849 Weston, 1993, Detection of polycyclic aromatic hydrocarbon-DNA adducts in human lung, Environ Health Perspect, 99, 257, 10.1289/ehp.9399257 Du, 2005, Formation of MTBE-DNA adducts in mice measured with accelerator mass spectrometry, Environ Toxicol, 20, 397, 10.1002/tox.20124 Snyderwine, 1988, Use of the P-32-postlabeling method to detect DNA adducts of 2-amino-3-methylimidazolo[4,5-F]quinoline (Iq) in monkeys fed Iq — identification of the N-(deoxyguanosin-8-Yl)-Iq adduct, Carcinogenesis, 9, 1739, 10.1093/carcin/9.10.1739 Gunter, 2007, Leukocyte polycyclic aromatic hydrocarbon-DNA adduct formation and colorectal adenoma, Carcinogenesis, 28, 1426, 10.1093/carcin/bgm022 Tilby, 1999, Measuring DNA adducts by immunoassay (ELISA), Methods Mol Med, 28, 121 Pratt, 2011, Polycyclic aromatic hydrocarbon (PAH) exposure and DNA adduct semi-quantitation in archived human tissues, Int J Environ Res Public Health, 8, 2675, 10.3390/ijerph8072675 Arlt, 2012, Exposure to benzo[a]pyrene of hepatic cytochrome P450 reductase null (HRN) and P450 reductase conditional null (RCN) mice: detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and 32P-postlabelling, Toxicol Lett, 213, 160, 10.1016/j.toxlet.2012.06.016 Culp, 1997, Immunochemical, 32P-postlabeling, and GC/MS detection of 4-aminobiphenyl-DNA adducts in human peripheral lung in relation to metabolic activation pathways involving pulmonary N-oxidation, conjugation, and peroxidation, Mutat Res, 378, 97, 10.1016/S0027-5107(97)00101-2 Weston, 1991, Fluorescence detection of benzo[a]pyrene--DNA adducts in human lung, Carcinogenesis, 12, 1445, 10.1093/carcin/12.8.1445 Min, 2015, Baicalin protects keratinocytes from toll-like receptor-4 mediated DNA damage and inflammation following ultraviolet irradiation, Photochem Photobiol, 91, 1435, 10.1111/php.12505 Min, 2008, Inhibitory effects of baicalin on ultraviolet B-induced photo-damage in keratinocyte cell line, Am J Chin Med, 36, 745, 10.1142/S0192415X0800620X Piao, 2013, Protective effect of fisetin (3,7,3′,4′-Tetrahydroxyflavone) against gamma-irradiation-induced oxidative stress and cell damage, Biomol Ther (Seoul), 21, 210, 10.4062/biomolther.2013.017 Kang, 2014, Fisetin attenuates hydrogen peroxide-induced cell damage by scavenging reactive oxygen species and activating protective functions of cellular glutathione system, In Vitro Cell Dev Biol Anim, 50, 66, 10.1007/s11626-013-9681-6 Sharma, 2014, Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells, PLoS One, 9, e91588, 10.1371/journal.pone.0091588 Wilms, 2005, Protection by quercetin and quercetin-rich fruit juice against induction of oxidative DNA damage and formation of BPDE-DNA adducts in human lymphocytes, Mutat Res, 582, 155, 10.1016/j.mrgentox.2005.01.006 Ramos, 2010, Protective effects of ursolic acid and luteolin against oxidative DNA damage include enhancement of DNA repair in Caco-2 cells, Mutat Res, 692, 6, 10.1016/j.mrfmmm.2010.07.004 Bestwick, 1740, The effect of short-term kaempferol exposure on reactive oxygen levels and integrity of human (HL-60) leukaemic cells, Biochim Biophys Acta, 2005, 340 Satyamitra, 2014, The antioxidant flavonoids, orientin and vicenin enhance repair of radiation-induced damage, SAJ Pharm Pharmacol, 1, 1 Bing-Rong, 2008, Protective effect of the baicalin against DNA damage induced by ultraviolet B irradiation to mouse epidermis, Photodermatol Photoimmunol Photomed, 24, 175, 10.1111/j.1600-0781.2008.00356.x Zhang, 2014, The protective effect of baicalin against UVB irradiation induced photoaging: an in vitro and in vivo study, PLoS One, 9, e99703, 10.1371/journal.pone.0099703 Qi, 2011, Protective effect of flavonoids from Astragalus complanatus on radiation induced damages in mice, Fitoterapia, 82, 383, 10.1016/j.fitote.2010.11.015 Marcolin, 2013, Quercetin decreases liver damage in mice with non-alcoholic steatohepatitis, Basic Clin Pharmacol Toxicol, 112, 385, 10.1111/bcpt.12049 Golla, 2014, Evaluation of antioxidant and DNA damage protection activity of the hydroalcoholic extract of Desmostachya bipinnata L, Sci World J, 2014, 215084, 10.1155/2014/215084 Shukla, 2006, Protection from radiation-induced mitochondrial and genomic DNA damage by an extract of Hippophae rhamnoides, Environ Mol Mutagen, 47, 647, 10.1002/em.20251 Gafrikova, 2014, Extract from Armoracia rusticana and its flavonoid components protect human lymphocytes against oxidative damage induced by hydrogen peroxide, Molecules, 19, 3160, 10.3390/molecules19033160 Bhullar, 2015, Antioxidant and cytoprotective properties of partridgeberry polyphenols, Food Chem, 168, 595, 10.1016/j.foodchem.2014.07.103