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Genotoxicity and Carcinogenicity of Herbal Products

  • Mélanie Poivre
  • Amandine Nachtergael
  • Valérian Bunel
  • Okusa Ndjolo Philippe
  • Pierre Duez
Chapter

Abstract

In 2012, the World Health Organization (WHO) recorded 14 million new cases of cancer and 8.2 million cancer-related deaths. Remarkably, the WHO estimates that 30 % of cancer mortalities are due to lifestyle choices and environmental factors that can and should be avoided. In line with these recommendations, this chapter discusses the genotoxicity and carcinogenicity of herbal products. Although often perceived as innocuous by the general public, many herbs harbor phytochemicals that are either directly reactive towards DNA or likely to disturb cellular homeostasis, cell cycle, and/or genome maintenance mechanisms; this may translate into genotoxicity, carcinogenicity, or co-carcinogenicity. Genotoxicity refers to the deleterious effect of a chemical compound or a physical event on the genetic material; such genotoxic events are considered hallmarks of cancer risk. Nevertheless, much of the damage to the genetic material can be efficiently bypassed and/or repaired by the numerous genome maintenance mechanisms of the cell and may not lead to cancer. The long-term safety evaluation is probably better investigated through carcinogenicity, which denotes the capacity of a chemical substance or a mixture of chemical substances to induce cancer or increase its incidence. The major mechanisms of carcinogenicity are discussed along with biomarkers and approved regulatory guidelines. The recent development of innovative carcinogenicity testing strategies, especially based on functional genomics, are debated and evaluated for possible application to the precocious evaluation of herbal products' long-term safety. Finally, this chapter provides some examples of proven or suspected carcinogenic herbal products reported in the current literature.

Keywords

Herbal products Medicinal plants Natural products Genotoxicity Carcinogenicity 

Abbreviations

2YRB

2-year rodent bioassay

AA

Aristolochic acid

AAN

Aristolochic acid nephropathy

BER

Base excision repair

CSC

Cancer stem cells

ECVAM

European Centre for the Validation of Alternative Methods

EMA

European Medicines Agency

FDA

Food and Drug Administration

HMP

Herbal medicinal products

HMPC

Committee on Herbal Medicinal Products

IARC

International Agency for Research on Cancer

ICH

International Conference on Harmonization

NER

Nucleotide excision repair

NOAEL

No observed adverse effect level

OECD

Organization for Economic Co-operation and Development

PA

Pyrrolizidine alkaloid

PFS

Plant food supplements

SAR

Structure-activity relationship

TCM

Traditional Chinese medicine

TFT

Trifluorothymidine

WHO

World Health Organization

References

  1. Abel G, Göggelmann W (1986) Genotoxic activity of ß-asarone and commercial calamus drugs. Mutat Res/Environ Mutagen Relat Sub 164(4):287Google Scholar
  2. Ames BN, Durston WE, Yamasaki E, Lee FD (1973) Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci USA 70(8):2281–2285PubMedPubMedCentralCrossRefGoogle Scholar
  3. Andrew AS, Burgess JL, Meza MM, Demidenko E, Waugh MG, Hamilton JW et al (2006) Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic. Environ Health Perspect 114(8):1193–1198PubMedPubMedCentralCrossRefGoogle Scholar
  4. Balmain A (2001) Cancer genetics: from Boveri and Mendel to microarrays. Nat Rev Cancer 1(1):77–82. doi: 10.1038/35094086 PubMedCrossRefGoogle Scholar
  5. Barnes J, Anderson L, Phillipson D (2007) Herbal medicines. 3rd edn. Press P, editor, LondonGoogle Scholar
  6. Bellakhdar J (1999) In: Press I (ed) La pharmacopée marocaine traditionnelle. Ibis Press, ParisGoogle Scholar
  7. van den Berg SJPL, Restani P, Boersma MG, Delmulle L, Rietjens IMCM (2011) Levels of genotoxic and carcinogenic ingredients in plant food supplements and associated risk assessment. Food Nutr Sci 02(09):989–1010CrossRefGoogle Scholar
  8. Bielas JH, Loeb KR, Rubin BP, True LD, Loeb LA (2006) Human cancers express a mutator phenotype. Proc Natl Acad Sci 103(48):18238–18242PubMedPubMedCentralCrossRefGoogle Scholar
  9. Billintona N, Hastwellb P, Beerensc D, Birrella L, Ellisb P, Maskelld S et al (2008) Interlaboratory assessment of the GreenScreen HC GADD45a-GFP genotoxicity screening assay: an enabling study for independent validation as an alternative method. Mutat Res 653(1–2):23–33CrossRefGoogle Scholar
  10. Borner FU, Schutz H, Wiedemann P (2011) The fragility of omics risk and benefit perceptions. Toxicol Lett 201:249–257PubMedCrossRefGoogle Scholar
  11. Botta A (2013) Relations entre génotoxicité, mutagenèse et cancérogenèse. In: l’Environnement IPMdSd (ed) Journées Nationales de Santé au Travail dans le BTP. Service Hospitalo-universitaire de Médecine et Santé au Travail, Marseille, pp 9–13Google Scholar
  12. Bruneton J (2005) Plantes toxiques: végétaux dangereux pour l'homme et les animaux. 3rd edn. Tec & Doc, editor. Lavoisier, ParisGoogle Scholar
  13. Bruneton J (2009a) Pharmacognosie, phytochimie, plantes médicinales 4e Ed. Lavoisier S.A.S., editor, CachanGoogle Scholar
  14. Bruneton J (2009b) Pharmacognosie: phytochimie, plantes médicinales. 4th edn. Lavoisier, editor, ParisGoogle Scholar
  15. Brusick D (1980) Principles of genetic toxicology. Plenum Press, New YorkCrossRefGoogle Scholar
  16. Burgio E, Migliore L (2015) Towards a systemic paradigm in carcinogenesis: linking epigenetics and genetics. Mol Biol Rep 42(4):777–790PubMedCrossRefGoogle Scholar
  17. Butterworth BE (2006) A classification framework and practical guidance for establishing a mode of action for chemical carcinogens. Regul Toxicol Pharmacol 45(1):9–23, Research Support, Non-U.S. Gov’tPubMedCrossRefGoogle Scholar
  18. Carcinogenesis Studies of Eugenol (1983) (CAS No. 97-53-0) in F344/N rats and B6C3F1 mice (Feed Studies). Natl Toxicol Program Tech Rep Ser 223:1–159Google Scholar
  19. Cassani-Galindo M, Madrigal-Bujaidar E, Chamorro G, Díaz F, Tamariz J, Espinosa-Aguirre J (2005) In vitro genotoxic evaluation of three α-asarone analogues. Toxicol Vitro 19(4):547–552Google Scholar
  20. Chamorro G, Garduño L, Martínez E, Madrigal E, Tamariz J, Salazar M (1998) Dominant lethal study of α-asarone in male mice. Toxicol Lett 99(2):71–77PubMedCrossRefGoogle Scholar
  21. Chan S (2003) Determination of aristolochic acids in medicinal plant and herbal product by liquid chromatography–electrospray–ion trap mass spectrometry. Talanta 60(4):679–685PubMedCrossRefGoogle Scholar
  22. Charles C, Chemais M, Stevigny C, Dubois J, Nachergael A, Duez P (2012) Measurement of the influence of flavonoids on DNA repair kinetics using the comet assay. Food Chem 135(4):2974–2981PubMedCrossRefGoogle Scholar
  23. Charles C, Nachtergael A, Ouedraogo M, Belayew A, Duez P (2014) Effects of chemopreventive natural products on non-homologous end-joining DNA double-strand break repair. Mutat Res/Genet Toxicol Environ Mutagen 768:33–41CrossRefGoogle Scholar
  24. Chen CL, Chi CW, Chang KW, Liu TY (1999) Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history. Carcinogenesis 20(12):2331–2334PubMedCrossRefGoogle Scholar
  25. Chen T, Mei N, Fu PP (2010) Genotoxicity of pyrrolizidine alkaloids. J Appl Toxicol 30(3):183–196PubMedGoogle Scholar
  26. Cheng K-F, Leung P-C (2012) Safety in Chinese medicine research. Open J Saf Sci Technol 2(01):32CrossRefGoogle Scholar
  27. Chung Y-T, Chen C-L, Wu C-C, Chan S-A, Chi C-W, Liu T-Y (2008) Safrole-DNA adduct in hepatocellular carcinoma associated with betel quid chewing. Toxicol Lett 183(1–3):21–27PubMedCrossRefGoogle Scholar
  28. Cleaver JE (2005) Cancer in xeroderma pigmentosum and related disorders of DNA repair. Nat Rev Cancer 5(7):564–573. doi: 10.1038/nrc1652 PubMedCrossRefGoogle Scholar
  29. Cohnheim J (1875) Congenitales, quergestreiftes muskelsarkom der nieren. Virchows Arch 65(1):64–69CrossRefGoogle Scholar
  30. Combes R (2012) In silico methods for toxicity prediction. In: Balls M, Combes R, Bhogal N (eds) New technologies for genotoxicity testing. Springer US, New York city. pp 96–116Google Scholar
  31. Council of Europe (2005) Estragole. In: Active principles (constituents of toxicological concern) contained in natural sources of flavouring. Council of Europe, StrasbourgGoogle Scholar
  32. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867. doi: 10.1038/nature01322 PubMedPubMedCentralCrossRefGoogle Scholar
  33. Daimon H, Sawada S, Asakura S, Sagami F (1998) In vivo genotoxicity and DNA adduct levels in the liver of rats treated with safrole. Carcinogenesis 19(1):141–146Google Scholar
  34. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S et al (2002) Mutations of the BRAF gene in human cancer. Nature 417(6892):949–954. doi: 10.1038/nature00766 PubMedCrossRefGoogle Scholar
  35. De Broe ME (2012) Chinese herbs nephropathy and Balkan endemic nephropathy: toward a single entity, aristolochic acid nephropathy. Kidney Int 81(6):513–515PubMedCrossRefGoogle Scholar
  36. Debelle FD, Vanherweghem JL, Nortier JL (2008) Aristolochic acid nephropathy: a worldwide problem. Kidney Int 74(2):158–169PubMedCrossRefGoogle Scholar
  37. Dixon K, Kopras E (2004) Genetic alterations and DNA repair in human carcinogenesis. Semin Cancer Biol 14(6):441–448PubMedCrossRefGoogle Scholar
  38. ECVAM (2015) European union reference laboratory for alternatives to animal testingGoogle Scholar
  39. EFSA (2009) Advice on the EFSA guidance document for the safety 505 assessment of botanicals and botanical preparations intended for use as food supplements, based on 506 real case studiesGoogle Scholar
  40. Ekor M (2014) The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. F Pharmacol [Review] 4(177):1–10Google Scholar
  41. EMEA (2008) Guideline on the assessment of genotoxicity of herbal substances/preparations. London [06/02/2014]; 4–11/2. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003569.pdf
  42. EMEA (2008) Guideline on the assessment of genotoxicity of herbal substances/preparations. London [20/04/2015]; Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003569.pdf
  43. European Commission: Scientific Committee on Food (2002) Opinion of the scientific committee on food on the safety of the presence of safrole (1-allyl-3,4-methylene dioxy benzene) in flavourings and other food ingredients with flavouring properties. European Commission, Brussels, Contract No.: SCF/CS/FLAV/FLAVOUR/6 ADD3Google Scholar
  44. FDA (2012) Guidance for industry S2(R1) genotoxicity testing and data interpretation for pharmaceuticals intended for human useGoogle Scholar
  45. Fjodorova N, Vračko M, Novič M, Roncaglioni A, Benfenati E (2010) New public QSAR model for carcinogenicity. Chem Central J 4(Suppl 1):S3CrossRefGoogle Scholar
  46. Friedberg EC, Wagner R, Radman M (2002) Specialized DNA polymerases, cellular survival, and the genesis of mutations. Science 296(5573):1627–1630PubMedCrossRefGoogle Scholar
  47. Fu P, Xia Q, Lin G, Chou M (2002) Genotoxic pyrrolizidine alkaloids − mechanisms leading to DNA adduct formation and tumorigenicity. Int J Mol Sci 3:948–964CrossRefGoogle Scholar
  48. Gokmen MR, Cosyns JP, Arlt VM, Stiborova M, Phillips DH, Schmeiser HH et al (2013) The epidemiology, diagnosis, and management of aristolochic acid nephropathy: a narrative review. Ann Intern Med 158(6):469–477PubMedCrossRefGoogle Scholar
  49. Gonzalez M, Bernad A (2012) Characteristics of adult stem cells. In: López-Larrea C, López-Vázquez A, Suárez-Álvarez B (eds) Stem cell transplantation. Springer-Verlag, New York, USA, pp 103–120Google Scholar
  50. Greene N (2002) Computer systems for the prediction of toxicity: an update. Adv Drug Deliv Rev 54:417–431PubMedCrossRefGoogle Scholar
  51. Guyton KZ, Kyle AD, Aubrecht J, Cogliano VJ, Eastmond DA, Jackson M et al (2009) Improving prediction of chemical carcinogenicity by considering multiple mechanisms and applying toxicogenomic approaches. Mutat Res/Rev Mutat Res 681(2–3):230–240CrossRefGoogle Scholar
  52. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70PubMedCrossRefGoogle Scholar
  53. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674PubMedCrossRefGoogle Scholar
  54. Hartung T (2011) From alternative methods to a new toxicology. Eur J Pharm Biopharm 77:338–349PubMedCrossRefGoogle Scholar
  55. Hasheminejad G, Caldwell J (1994) Genotoxicity of the alkenylbenzenes α- and β-asarone, myristicin and elemicin as determined by the UDS assay in cultured rat hepatocytes. Food Chem Toxicol 32(3):223–231PubMedCrossRefGoogle Scholar
  56. Heinrich M, Chan J, Wanke S, Neinhuis C, Simmonds MS (2009) Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2 – A global assessment based on bibliographic sources. J Ethnopharmacol 125(1):108–144PubMedCrossRefGoogle Scholar
  57. Hernandez LG, van Steeg H, Luijten M, van Benthem J (2009) Mechanisms of non-genotoxic carcinogens and importance of a weight of evidence approach. Mutat Res [Review] 682(2–3):94–109CrossRefGoogle Scholar
  58. Hesketh R (1997) The oncogene & tumour suppressor gene factsbook. In: Hesketh R (ed) Academic press, San DiegoGoogle Scholar
  59. Hoet P, Godderis L (2013) Genotoxicity and mutagenicity testing: a brief overview of the main tests, pitfalls and regulatory framework. In: BEMS- Belgian Environmental Mutagen Society B (ed) Toxicology as the scientific basis for management of chemical risk. BEMS, ElewijtGoogle Scholar
  60. Homburger F, Bogdonoff PD, Kelley TF (1965) Influence of diet on chronic oral toxicity of Safrole and butter yellow in rats. Proc Soc Exp Biol Med 119(4):1106–1110PubMedCrossRefGoogle Scholar
  61. Howes AJ, Chan VSW, Caldwell J (1990) Structure-specificity of the genotoxicity of some naturally occurring alkenylbenzenes determined by the unscheduled DNA synthesis assay in rat hepatocytes. Food Chem Toxicol 28(8):537–542PubMedCrossRefGoogle Scholar
  62. Hubaux R, Becker-Santos DD, Enfield KSS, Rowbotham D, Lam S, Lam WL et al (2013) Molecular features in arsenic-induced lung tumors. Mol Cancer 12:20PubMedPubMedCentralCrossRefGoogle Scholar
  63. IARC (2002) Rubia tinctorium, Morinda officinalis and anthraquinones. IARC Monogr Eval Carcinog Risks Hum 82:129–151, Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and StyreneGoogle Scholar
  64. IARC (2004) Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. IARC Monogr Eval Carcinog Risks Hum 85:1–334Google Scholar
  65. IARC (2015) International agency for research on cancer: agents classified by the IARC monographs. Available from: http://monographs.iarc.fr/ENG/Classification/
  66. ICH (2014) Guidance for industry S2B genotoxicity: a standard battery for genotoxicity testing of pharmaceuticals. [03/02/2014]. Available from: http://www.ich.org/products/guidelines
  67. ICH (2015) Guideline on the need for carcinogenicity studies of pharmaceuticals S1A S1A. Available from: http://www.ich.org/products/guidelines
  68. ICH (2015) International conference on harmonisation: testing for carcinogenicity of pharmaceuticals S1B. Available from: http://www.ich.org/products/guidelines
  69. Jacobson-Kram D (2009) Cancer risk assessment approaches at the FDA/CDER: is the era of the 2-year bioassay drawing to a close? Toxicol Pathol 38(1):169–170PubMedCrossRefGoogle Scholar
  70. Kahumba JRT, Okusa PN, Bakari A, Bizumukama L, Kalonji J-B, Kiendrebeogo M, Rabemenantsoa C, El Jaziri M, Williamson EM, Duez P (2015) Traditional African medicine: from ancestral knowledge to a modern integrated future? Science 350(6262):S61–S63Google Scholar
  71. Kawai K, Mori H, Sugie S, Yoshimi N, Inoue T, Nakamaru T et al (1986) Genotoxicity in the hepatocyte/DNA repair test and toxicity to liver mitochondria of 1-hydroxyanthraquinone and several dihydroxyanthraquinones. Cell Biol Toxicol 2(4):457–467PubMedCrossRefGoogle Scholar
  72. Kevekordes S, Spielberger J, Burghaus C, Birkenkamp P, Zietz B, Paufler P et al (2001) Micronucleus formation in human lymphocytes and in the metabolically competent human hepatoma cell line Hep-G2: results with 15 naturally occurring substances. Anticancer Res 21(1A):461–469PubMedGoogle Scholar
  73. Knudson AG (2001) Two genetic hits (more or less) to cancer. Nat Rev Cancer 1(2):157–162. doi: 10.1038/35101031 PubMedCrossRefGoogle Scholar
  74. Langel D, Ober D, Pelser PB (2010) The evolution of pyrrolizidine alkaloid biosynthesis and diversity in the Senecioneae. Phytochem Rev 10(1):3–74CrossRefGoogle Scholar
  75. Li X, Wang H (2004) Aristolochic acid nephropathy: what we know and what we have to do. Nephrology (Carlton) 9(3):109–111CrossRefGoogle Scholar
  76. Liu X, Wang Q, Song G, Zhang G, Ye Z, Williamson EM (2014) The classification and application of toxic Chinese materia medica. Phytother Res 28(3):334–347PubMedCrossRefGoogle Scholar
  77. Loeb LA (2011) Human cancers express mutator phenotypes: origin, consequences and targeting. Nat Rev Cancer 11(6):450–457. doi: 10.1038/nrc3063 PubMedPubMedCentralCrossRefGoogle Scholar
  78. Loeb LA, Harris CC (2008) Advances in chemical carcinogenesis: a historical review and prospective. Cancer Res 68(17):6863–6872PubMedPubMedCentralCrossRefGoogle Scholar
  79. Loeb LA, Springgate CF, Battula N (1974) Errors in DNA replication as a basis of malignant changes. Cancer Res 34(9):2311–2321PubMedGoogle Scholar
  80. Mädge I, Cramer L, Rahaus I, Jerz G, Winterhalter P, Beuerle T (2015) Pyrrolizidine alkaloids in herbal teas for infants, pregnant or lactating women. Food Chem 187:491–498PubMedCrossRefGoogle Scholar
  81. Magdolenova Z, Collins A, Kumar A, Dhawan A, Stone V, Dusinska M (2014) Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology 8(3):233–278Google Scholar
  82. Marczewska J, Drozd E, Anuszewska E, Chilmonczyk Z, Łozowicka B (2013) Assessment of the genotoxic activity of alpha-asarone and its derivatives in the comet assay. Acta Pol Pharm 70(2):349–354PubMedGoogle Scholar
  83. Martinez-Arribas F, Alvarez T, Del Val G, Martin-Garabato E, Nunez-Villar M-J, Lucas R et al (2007) Bcl-2 expression in breast cancer: a comparative study at the mRNA and protein level. Anticancer Res 27(1A):219–222PubMedGoogle Scholar
  84. Marx J (2002) Debate surges over the origins of genomic defects in cancer. Science 29(5581):544–546CrossRefGoogle Scholar
  85. Maurici D, Aardema M, Corvi R, Kleber M, Krul C, Laurent C et al (2004) Timetables for the phasing-out of animal testing in the framework of the 7th amendment to the cosmetics directive: genotoxicity and mutagenicity. Commission of the European Communities, BrusselsGoogle Scholar
  86. Mei N, Arlt VM, Phillips DH, Heflich RH, Chen T (2006) DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver. Mutat Res/Fundam Mol Mech Mutagen 602(1–2):83–91CrossRefGoogle Scholar
  87. Michl J, Jennings HM, Kite GC, Ingrouille MJ, Simmonds MSJ, Heinrich M (2013) Is aristolochic acid nephropathy a widespread problem in developing countries? A case study of Aristolochia indica L. in Bangladesh using an ethnobotanical–phytochemical approach. J Ethnopharmacol 149(1):235–244PubMedCrossRefGoogle Scholar
  88. Michl J, Ingrouille MJ, Simmonds MS, Heinrich M (2014) Naturally occurring aristolochic acid analogues and their toxicities. Nat Prod Rep 31(5):676–693PubMedCrossRefGoogle Scholar
  89. Migheli F, Migliore L (2014) Epigenetic perturbations in the context of the multi-hit hypothesis of carcinogenesis. In: Maulik N, Karagiannis T (eds) Molecular mechanisms and physiology of disease. Springer, New York, pp 383–399Google Scholar
  90. Miller JA, Miller EC (1976) Carcinogens occurring naturally in foods. Fed Proc 35(6):1316–1321PubMedGoogle Scholar
  91. Monier R (2008) News in carcinogenesis. C R Biol 331(2):101–103PubMedCrossRefGoogle Scholar
  92. Morales-Ramírez P, Madrigal-Bujaidar E, Mercader-Martínez J, Cassini M, González G, Chamorro-Cevallos G et al (1992) Sister-chromatid exchange induction produced by in vivo and in vitro exposure to alpha-asarone. Mutat Res/Genet Toxicol Environ Mutagen 279(4):269–273Google Scholar
  93. Muller L, Kikuchi Y, Probst G, Schechtman L, Shimada H, Sofuni T et al (1999) ICH-Harmonised guidances on genotoxicity testing of pharmaceuticals: evolution, reasoning and impact. Mutat Res 436:195–225PubMedCrossRefGoogle Scholar
  94. Muller J, Decordier I, Hoet PH, Lombaert N, Thomassen L, Huaux F et al (2008) Clastogenic and aneugenic effects of multi-wall carbon nanotubes in epithelial cells. Carcinogenesis 29(2):427–433PubMedCrossRefGoogle Scholar
  95. Mulware SJ (2012) Trace elements and carcinogenicity: a subject in review. 3 Biotech 3(2):85–96PubMedCentralCrossRefGoogle Scholar
  96. Munerato MC, Sinigaglia M, Reguly ML, de Andrade HH (2005) Genotoxic effects of eugenol, isoeugenol and safrole in the wing spot test of Drosophila melanogaster. Mutat Res 582(1–2):87–94PubMedCrossRefGoogle Scholar
  97. Nachtergael A, Charles C, Spanoghe M, Gadenne M, Belayew A, Duez P (2013) Measurement of translesion synthesis by fluorescent capillary electrophoresis: 7, 8-Dihydro-8-oxodeoxyguanosine bypass modulation by natural products. Anal Biochem 440(1):23–31PubMedCrossRefGoogle Scholar
  98. Nachtergael A, Poivre M, Belayew A, Duez P (2015) In vitro genotoxicity tests point to an unexpected and harmful effect of a Magnolia and Aristolochia association. J Ethnopharmacol 174(C):178–186PubMedCrossRefGoogle Scholar
  99. NAP (2007) Applications of toxicogenomic technologies to predictive toxicology and risk assessment. Press NA, editor, WashingtonGoogle Scholar
  100. National Cancer Institute NIH (2015) Tumor microenvironment national institute of health; [22/04/2015]. Available from: http://www.cancer.gov/dictionary?cdrid=561725
  101. National Toxicology Program (2011) Danthron. Rep Carcinog 12:128–129Google Scholar
  102. Niir (2003) In: Research NIaN (ed) The complete technology book of essential oils (aromatic chemicals), 1st edn. Asia Pacific Business Press, DelhiGoogle Scholar
  103. Nortier JL, Vanherweghem JL (2002) Renal interstitial fibrosis and urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). Toxicology 181–182:577–580PubMedCrossRefGoogle Scholar
  104. Nortier JL, Martinez MC, Schmeiser HH, Arlt VM, Bieler CA, Petein M et al (2000) Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med 342(23):1686–1692PubMedCrossRefGoogle Scholar
  105. Nortier J, Pozdzik A, Roumeguere T, Vanherweghem J-L (2013) Néphropathie aux acides aristolochiques (“néphropathie aux herbes chinoises”). EMC – Néphrologie 10(2):1–14CrossRefGoogle Scholar
  106. NTP (2000) NTP toxicology and carcinogenesis studies of methyleugenol (CAS NO. 93-15-2) in F344/N rats and B6C3F1 mice (gavage studies). Natl Toxicol Program Tech Rep Ser 491:1–412Google Scholar
  107. Nutraceuticals World (2012) Global herbal supplement market to reach $107 billion by 2017 [29/04/2015]. Available from: http://www.nutraceuticalsworld.com/contents/view_breaking-news/2012-03-07/global-herbal-supplement-market-to-reach-107-billion-by-2017
  108. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106–110. doi: 10.1038/nature05372 PubMedCrossRefGoogle Scholar
  109. OECD (2007) Detailed review paper on cell transformation assays for detection of chemical carcinogens. In: Environment O (ed) Health and Safety PublicationsGoogle Scholar
  110. Ouedraogo M, Baudoux T, Stévigny C, Nortier J, Colet J-M, Efferth T et al (2012) Review of current and “omics” methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms. J Ethnopharmacol 140(3):492–512PubMedCrossRefGoogle Scholar
  111. Pelkonen O, Xu Q, Fan T-P (2014) Why is research on herbal medicinal products important and how can we improve its quality? J Tradit Complement Med 4(1):1–7PubMedPubMedCentralCrossRefGoogle Scholar
  112. Quante M, Wang TC (2008) Inflammation and stem cells in gastrointestinal carcinogenesis. Physiology (Bethesda) 23:350–359CrossRefGoogle Scholar
  113. Raghava GPS, Gusenleitner D, Auerbach SS, Melia T, Gómez HF, Sherr DH et al (2014) Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action. PLoS One 9(7):e102579CrossRefGoogle Scholar
  114. Randerath K, Liehr JG, Gladek A, Randerath E (1989) Use of the 32P-postlabelling assay to study transplacental carcinogens and transplacental carcinogenesis. IARC Sci Publ 96:189–205Google Scholar
  115. Randerath K, Putman KL, Randerath E (1993) Flavor constituents in cola drinks induce hepatic DNA adducts in adult and fetal mice. Biochem Biophys Res Commun 192(1):61–68PubMedCrossRefGoogle Scholar
  116. Rizwani W, Chellappan S (2009) In vitro replication assay with Mammalian cell extracts. In: Chellappan S (ed) Chromatin protocols. Humana Press, New York city. pp 203–216Google Scholar
  117. Rodriguez-Paez L, Juárez-Sanchez M, Antúnez-Solís J, Baeza I, Wong C (2003) Alpha-asarone inhibits HMG-CoA reductase, lowers serum LDL-cholesterol levels and reduces biliary CSI in hypercholesterolemic rats. Phytomedicine 10(5):397–404PubMedCrossRefGoogle Scholar
  118. Rossman TG (2003) Mechanism of arsenic carcinogenesis: an integrated approach. Mutat Res/Fundam Mol Mech Mutagen 533(1):37–65CrossRefGoogle Scholar
  119. Sarasin A (2003) An overview of the mechanisms of mutagenesis and carcinogenesis. Mutat Res/Rev Mutat Res 544(2–3):99–106CrossRefGoogle Scholar
  120. Segelman AB, Segelman FP, Karliner J, Sofia RD (1976) Sassafras and herb tea. Potential health hazards. JAMA 236(5):477PubMedCrossRefGoogle Scholar
  121. Shaked Y, Ciarrocchi A, Franco M, Lee CR, Man S, Cheung AM et al (2006) Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors. Science 313(5794):1785–1787PubMedCrossRefGoogle Scholar
  122. Shen S, Wang C, Weinfeld M, Le XC (2013) Inhibition of nucleotide excision repair by arsenic. Chin Sci Bull 58(2):214–221CrossRefGoogle Scholar
  123. Smith K (1992) Spontaneous mutagenesis: experimental, genetic and other factors. Mutat Res 277(2):139–162PubMedCrossRefGoogle Scholar
  124. Taylor JM, Jones WI, Hagan EC, Gross MA, Davis DA, Cook EL (1967) Toxicity of oil of calamus (Jammu variety). Toxicol Appl Pharmacol 10(2):378–411CrossRefGoogle Scholar
  125. Thomas SJ, MacLennan R (1992) Slaked lime and betel nut cancer in Papua New Guinea. Lancet 340(8819):577–578PubMedCrossRefGoogle Scholar
  126. Tomasetti C, Vogelstein B (2015) Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347(6217):78–81PubMedPubMedCentralCrossRefGoogle Scholar
  127. U.S. Food and Drug Administration (1973) Database of select committee on GRAS substances (SCOGS) reviews: nutmeg and mace. FDA, Silver SpringGoogle Scholar
  128. Ueng YF, Hsieh CH, Don MJ, Chi CW, Ho LK (2004) Identification of the main human cytochrome P450 enzymes involved in safrole 1′-hydroxylation. Chem Res Toxicol 17(8):1151–1156PubMedCrossRefGoogle Scholar
  129. Unger P, Melzig MF (2012) Comparative study of the cytotoxicity and genotoxicity of alpha- and beta-asarone. Sci Pharm 80(3):663–668PubMedPubMedCentralCrossRefGoogle Scholar
  130. Valerio LG Jr (2009) In-silico toxicology for the pharmaceutical sciences. Toxicol Appl Pharmacol 241:356–370PubMedCrossRefGoogle Scholar
  131. Vanherweghem JL, Tielemans C, Abramowicz D, Depierreux M, Vanhaelen-Fastre R, Vanhaelen M et al (1993) Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet 341(8842):387–391PubMedCrossRefGoogle Scholar
  132. Vineis P, Schatzkin A, Potter JD (2010) Models of carcinogenesis: an overview. Carcinogenesis 31(10):1703–1709PubMedPubMedCentralCrossRefGoogle Scholar
  133. Virchow R (1855) Editorial Archive fuer pathologische. Anatomie und Physiologie fuer klinische Medizin 8:23–54Google Scholar
  134. Walmsley RM, Billinton N (2011) How accurate is in vitro prediction of carcinogenicity? Br J Pharmacol 162(6):1250–1258PubMedPubMedCentralCrossRefGoogle Scholar
  135. Wang T-L, Rago C, Silliman N, Ptak J, Markowitz S, Willson JKV et al (2002) Prevalence of somatic alterations in the colorectal cancer cell genome. Proc Natl Acad Sci 99(5):3076–3080PubMedPubMedCentralCrossRefGoogle Scholar
  136. Wang YP, Yan J, Beger RD, Fu PP, Chou MW (2005a) Metabolic activation of the tumorigenic pyrrolizidine alkaloid, monocrotaline, leading to DNA adduct formation in vivo. Cancer Lett 226(1):27–35 [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S.]PubMedCrossRefGoogle Scholar
  137. Wang Y-P, Yan J, Fu PP, Chou MW (2005b) Human liver microsomal reduction of pyrrolizidine alkaloid N-oxides to form the corresponding carcinogenic parent alkaloid. Toxicol Lett 155(3):411–420PubMedCrossRefGoogle Scholar
  138. Williams GM, Iatropoulos MJ, Jeffrey AM, Duan JD (2013) Methyleugenol hepatocellular cancer initiating effects in rat liver. Food Chem Toxicol 53:187–196PubMedCrossRefGoogle Scholar
  139. Wislocki PG, Miller EC, Miller JA, McCoy EC, Rosenkranz HS (1977) Carcinogenic and mutagenic activities of safrole, 1′-hydroxysafrole, and some known or possible metabolites. Cancer Res 37(6):1883–1891PubMedGoogle Scholar
  140. Wu J, Starr S (2014) Low-fidelity compensatory backup alternative DNA repair pathways may unify current carcinogenesis theories. Future Oncol 10(7):1239–1253PubMedCrossRefGoogle Scholar
  141. Wu S, Powers S, Zhu W, Hannun YA (2016) Substantial contribution of extrinsic risk factors to cancer development. Nature 529(7584):43–47PubMedCrossRefGoogle Scholar
  142. Xia Q, Yan J, Chou MW, Fu PP (2008) Formation of DHP-derived DNA adducts from metabolic activation of the prototype heliotridine-type pyrrolizidine alkaloid, heliotrine. Toxicol Lett 178(2):77–82, Research Support, U.S. Gov’t, Non-P.H.SPubMedCrossRefGoogle Scholar
  143. Yamani A, Bunel V, Antoine M-H, Husson C, Stévigny C, Duez P et al (2015) Substitution between Aristolochia and Bryonia genus in North-Eastern Morocco: toxicological implications. J Ethnopharmacol 166:250–260PubMedCrossRefGoogle Scholar
  144. Zhang HL, Zhang QW, Zhang XQ, Ye WC, Wang YT (2010) Chemical constituents from the roots of Morinda officinalis. Chin J Nat Med 8(10):1–4CrossRefGoogle Scholar
  145. Zhou J, Ouedraogo M, Qu F, Duez P (2013) Potential genotoxicity of traditional Chinese medicinal plants and phytochemicals: an overview. Phytother Res 27(12):1745–1755PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Mélanie Poivre
    • 1
  • Amandine Nachtergael
    • 1
  • Valérian Bunel
    • 1
    • 2
  • Okusa Ndjolo Philippe
    • 1
  • Pierre Duez
    • 1
  1. 1.Unit of Therapeutic Chemistry and Pharmacognosy, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and TechnologyUniversity of Mons – UMONSMonsBelgium
  2. 2.Laboratory of Pharmacognosy, Bromatology and Human Nutrition, Faculty of PharmacyUniversité Libre de Bruxelles – ULBBrusselsBelgium

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