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Journal of Biomedicine and Biotechnology
Volume 2012, Article ID 790987, 7 pages
http://dx.doi.org/10.1155/2012/790987
Review Article

On Enzyme-Based Anticancer Molecular Dietary Manipulations

Molecular Toxicology Unit, Department of Pharmacology, Alma-Mater Studiorum, Università di Bologna, Via Irnerio 48, 40126 Bologna, Italy

Received 21 February 2012; Accepted 3 August 2012

Academic Editor: Regine Schneider-Stock

Copyright © 2012 Andrea Sapone et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. C. Bailar and H. L. Gornik, “Cancer undefeated,” New England Journal of Medicine, vol. 336, no. 22, pp. 1569–1574, 1997. View at Publisher · View at Google Scholar · View at Scopus
  2. J. M. McGinnis and W. H. Foege, “Actual causes of death in the United States,” Journal of the American Medical Association, vol. 270, no. 18, pp. 2207–2212, 1993. View at Publisher · View at Google Scholar · View at Scopus
  3. A. Wicki and J. Hagmann, “Diet and cancer,” Swiss Medical Weekly, vol. 141, Article ID 13250, 2011. View at Google Scholar
  4. N. Khan, F. Afaq, and H. Mukhtar, “Lifestyle as risk factor for cancer: evidence from human studies,” Cancer Letters, vol. 293, no. 2, pp. 133–143, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. World Cancer Research Foundation and American Institute for Cancer Research, Food nutrition and the prevention of cancer: a global perspective, World Cancer Research Foundation and American Institute for Cancer Research, Washington, DC, USA, 1997.
  6. T. A. Woyengo, V. R. Ramprasath, and P. J. H. Jones, “Anticancer effects of phytosterols,” European Journal of Clinical Nutrition, vol. 63, no. 7, pp. 813–820, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. American Cancer Society Advisory Committee on Diet, “Nutrition and cancer prevention,” CA Cancer Journal for Clinicians, vol. 46, pp. 325–341, 1996. View at Google Scholar
  8. M. Nestle, “Dietary recommendations for cancer prevention: public policy implementation,” Journal of the National Cancer Institute. Monographs, no. 12, pp. 153–157, 1992. View at Google Scholar · View at Scopus
  9. M. Nestle, “Broccoli sprouts as inducers of carcinogen-detoxifying enzyme systems: clinical, dietary, and policy implications,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 21, pp. 11149–11151, 1997. View at Publisher · View at Google Scholar · View at Scopus
  10. S. N. Saldanha and T. O. Tollefsbol, “The role of nutraceuticals in chemoprevention and chemotherapy and their clinical outcomes,” Journal of Oncology, vol. 2012, Article ID 192464, 23 pages, 2012. View at Publisher · View at Google Scholar
  11. R. Peto, R. Doll, J. D. Buckley, and M. B. Sporn, “Can dietary beta-carotene materially reduce human cancer rates?” Nature, vol. 290, no. 5803, pp. 201–213, 1981. View at Google Scholar · View at Scopus
  12. L. W. Wattenberg, “Chemoprevention of cancer,” Cancer Research, vol. 45, no. 1, pp. 1–8, 1985. View at Google Scholar · View at Scopus
  13. M. A. Morse and G. D. Stoner, “Cancer chemoprevention: principles and prospects,” Carcinogenesis, vol. 14, no. 9, pp. 1737–1746, 1993. View at Google Scholar · View at Scopus
  14. C. Gerhäuser, M. You, J. Liu et al., “Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane that induces phase 2 drug-metabolizing enzymes,” Cancer Research, vol. 57, no. 2, pp. 272–278, 1997. View at Google Scholar · View at Scopus
  15. T. Shimada, “Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons,” Drug metabolism and pharmacokinetics, vol. 21, no. 4, pp. 257–276, 2006. View at Publisher · View at Google Scholar · View at Scopus
  16. V. A. Dadali and V. G. Makarov, “Biologically active substances from medicinal plants as a factor of the organism detoxication,” Voprosy Pitaniia, vol. 72, no. 5, pp. 49–55, 2003. View at Google Scholar · View at Scopus
  17. L. Vereczkey, K. Jemnitz, and Z. Gregus, “Human drug metabolizing enzymes II. Conjugation enzymes,” Acta Pharmaceutica Hungarica, vol. 68, no. 5, pp. 284–288, 1998. View at Google Scholar · View at Scopus
  18. T. Prestera, W. D. Holtzclaw, Y. Zhang, and P. Talalay, “Chemical and molecular regulation of enzymes that detoxify carcinogens,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 7, pp. 2965–2969, 1993. View at Google Scholar · View at Scopus
  19. G. J. Kelloff, C. W. Boone, J. A. Crowell et al., “New agents for cancer chemoprevention,” Journal of Cellular Biochemistry, vol. 63, no. 26, pp. 1–28, 1996. View at Google Scholar · View at Scopus
  20. C. Gerhauser, M. You, and J. Liu, “Chemopreventive potential of a novel sulforaphane analog,” The Proceedings of the American Association for Cancer Research, vol. 37, article A189, 1996. View at Google Scholar
  21. Y. Zhang, T. W. Kensler, C. G. Cho, G. H. Posner, and P. Talalay, “Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 8, pp. 3147–3150, 1994. View at Google Scholar · View at Scopus
  22. Y. Zhang and P. Talalay, “Mechanism of differential potencies of isothiocyanates as inducers of anticarcinogenic Phase 2 enzymes,” Cancer Research, vol. 58, no. 20, pp. 4632–4639, 1998. View at Google Scholar · View at Scopus
  23. M. Jang, L. Cai, G. O. Udeani et al., “Cancer chemopreventive activity of resveratrol, a natural product derived from grapes,” Science, vol. 275, no. 5297, pp. 218–220, 1997. View at Google Scholar · View at Scopus
  24. D. T. H. Verhoeven, H. Verhagen, R. A. Goldbohm, P. A. Van Den Brandt, and G. Van Poppel, “A review of mechanisms underlying anticarcinogenicity by brassica vegetables,” Chemico-Biological Interactions, vol. 103, no. 2, pp. 79–129, 1997. View at Publisher · View at Google Scholar · View at Scopus
  25. D. T. H. Verhoeven, R. A. Goldbohm, G. Van Poppel, H. Verhagen, and P. A. Van Den Brandt, “Epidemiological studies on Brassica vegetables and cancer risk,” Cancer Epidemiology Biomarkers and Prevention, vol. 5, no. 9, pp. 733–748, 1996. View at Google Scholar · View at Scopus
  26. I. Herr and M. W. Büchler, “Dietary constituents of broccoli and other cruciferous vegetables: implications for prevention and therapy of cancer,” Cancer Treatment Reviews, vol. 36, no. 5, pp. 377–383, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. H. Steinkellner, S. Rabot, C. Freywald et al., “Effects of cruciferous vegetables and their constituents on drug metabolizing enzymes involved in the bioactivation of DNA-reactive dietary carcinogens,” Mutation Research, vol. 480-481, pp. 285–297, 2001. View at Google Scholar · View at Scopus
  28. J. W. Lampe and S. Peterson, “Brassica, biotransformation and cancer risk: genetic polymorphisms alter the preventive effects of cruciferous vegetables,” Journal of Nutrition, vol. 132, no. 10, pp. 2991–2994, 2002. View at Google Scholar · View at Scopus
  29. X. L. Tan and S. D. Spivack, “Dietary chemoprevention strategies for induction of phase II xenobiotic-metabolizing enzymes in lung carcinogenesis: a review,” Lung Cancer, vol. 65, no. 2, pp. 129–137, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Barcelo, J. M. Gardiner, A. Gescher, and J. K. Chipman, “CYP2E1-mediated mechanism of anti-genotoxicity of the broccoli constituent sulforaphane,” Carcinogenesis, vol. 17, no. 2, pp. 277–282, 1996. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Faulkner, R. Mithen, and G. Williamson, “Selective increase of the potential anticarcinogen 4-methylsulphinylbutyl glucosinolate in broccoli,” Carcinogenesis, vol. 19, no. 4, pp. 605–609, 1998. View at Publisher · View at Google Scholar · View at Scopus
  32. P. P. Tadi, R. W. Teel, and B. H. S. Lau, “Organosulfur compounds of garlic modulate mutagenesis, metabolism, and DNA binding of aflatoxin B1,” Nutrition and Cancer, vol. 15, no. 2, pp. 87–95, 1991. View at Google Scholar · View at Scopus
  33. J. Y. Hong, T. Smith, M. J. Lee et al., “Metabolism of carcinogenic nitrosamines by rat nasal mucosa and the effect of diallyl sulfide,” Cancer Research, vol. 51, no. 5, pp. 1509–1514, 1991. View at Google Scholar · View at Scopus
  34. J. Hernaez, M. Xu, and R. Dashwood, “Effects of tea and chlorophyllin on the mutagenicity of N-hydroxy-IQ: studies of enzyme inhibition, molecular complex formation, and degradation/ scavenging of the active metabolites,” Environmental and Molecular Mutagenesis, vol. 30, pp. 468–474, 1997. View at Google Scholar
  35. M. Paolini, “Brussels sprouts: an exceptionally rich source of ambiguity for anticancer strategies,” Toxicology and Applied Pharmacology, vol. 152, no. 2, pp. 293–294, 1998. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Paolini and M. S. Legato, “Healthy broccoli?” Nature, vol. 357, no. 6378, p. 448, 1992. View at Google Scholar · View at Scopus
  37. A. Murakami and K. Ohnishi, “Target molecules of food phytochemicals: food science bound for the next dimension,” Food Function, vol. 3, pp. 462–476, 2012. View at Google Scholar
  38. S. Brünen, P. D. Vincent, and P. Baumann, “Therapeutic drug monitoring for drugs used in the treatment of substance-related disorders: literature review using a therapeutic drug monitoring appropriateness rating scale,” Therapeutic Drug Monitoring, vol. 33, pp. 561–572, 2011. View at Google Scholar
  39. L. Pendyala, G. Schwartz, W. Bolanowska-Higdon et al., “Phase I/pharmacodynamic study of N-acetylcysteine/oltipraz in smokers: early termination due to excessive toxicity,” Cancer Epidemiology Biomarkers and Prevention, vol. 10, no. 3, pp. 269–272, 2001. View at Google Scholar · View at Scopus
  40. G. Cantelli-Forti, P. Hrelia, and M. Paolini, “The pitfall of detoxifying enzymes,” Mutation Research, vol. 402, no. 1-2, pp. 179–183, 1998. View at Publisher · View at Google Scholar · View at Scopus
  41. F. P. Guengerich and D. C. Liebler, “Enzymatic activation of chemicals to toxic metabolites,” Critical Reviews in Toxicology, vol. 14, no. 3, pp. 259–307, 1985. View at Google Scholar · View at Scopus
  42. Y. Hu, S. L. Kabler, A. H. Tennant, A. J. Townsend, and A. D. Kligerman, “Induction of DNA-protein crosslinks by dichloromethane in a V79 cell line transfected with the murine glutathione-S-transferase theta 1 gene,” Mutation Research, vol. 607, no. 2, pp. 231–239, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. P. J. Sherratt, S. Williams, J. Foster, N. Kernohan, T. Green, and J. D. Hayes, “Direct comparison of the nature of mouse and human GST T1-1 and the implications on dichloromethane carcinogenicity,” Toxicology and Applied Pharmacology, vol. 179, no. 2, pp. 89–97, 2002. View at Publisher · View at Google Scholar · View at Scopus
  44. P. J. Sherratt, D. J. Pulford, D. J. Harrison, T. Green, and J. D. Hayes, “Evidence that human class Theta glutathione S-transferase T1-1 can catalyse the activation of dichloromethane, a liver and lung carcinogen in the mouse: comparison of the tissue distribution of GST T1-1 with that of classes Alpha, Mu and Pi GST in human,” Biochemical Journal, vol. 326, no. 3, pp. 837–846, 1997. View at Google Scholar · View at Scopus
  45. P. J. Sherratt, M. M. Manson, A. M. Thomson et al., “Increased bioactivation of dihaloalkanes in rat liver due to induction of class Theta glutathione S-transferase T1-1,” Biochemical Journal, vol. 335, no. 3, pp. 619–630, 1998. View at Google Scholar · View at Scopus
  46. E. Hallier, K. R. Schroder, K. Asmuth, A. Dommermuth, B. Aust, and H. W. Goergens, “Metabolism of dichloromethane (methylene chloride) to formaldehyde in human erythrocytes: influence of polymorphism of glutathione transferase Theta (GST T1-1),” Archives of Toxicology, vol. 68, no. 7, pp. 423–427, 1994. View at Publisher · View at Google Scholar · View at Scopus
  47. J. B. Wheeler, N. V. Stourman, R. Thier et al., “Conjugation of haloalkanes by bacterial and mammalian glutathione transferases: mono- and vicinal dihaloethanes,” Chemical Research in Toxicology, vol. 14, no. 8, pp. 1107–1117, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. S. H. Cho and F. P. Guengerich, “Conjugation of butadiene diepoxide with glutathione yields DNA adducts in vitro and in vivo,” Chemical Research in Toxicology, vol. 25, no. 3, pp. 706–712, 2012. View at Google Scholar
  49. G. A. Marsch, S. Botta, M. V. Martin, W. A. McCormick, and F. P. Guengerich, “Formation and mass spectrometric analysis of DNA and nucleoside adducts by S-(1-acetoxymethyl)glutathione and by glutathione S-transferase-mediated activation of dihalomethanes,” Chemical Research in Toxicology, vol. 17, no. 1, pp. 45–54, 2004. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Hesse, B. Jernstrom, and M. Martinez, “Inhibition of binding of benzo(a)pyrene metabolites to nuclear DNA by glutathione and glutathione S-transferase B,” Biochemical and Biophysical Research Communications, vol. 94, no. 2, pp. 612–617, 1980. View at Google Scholar · View at Scopus
  51. M. F. Kayser and S. Vuilleumier, “Dehalogenation of dichloromethane by dichloromethane dehalogenase/glutathione S-transferase leads to formation of DNA adducts,” Journal of Bacteriology, vol. 183, no. 17, pp. 5209–5212, 2001. View at Publisher · View at Google Scholar · View at Scopus
  52. D. H. Kim, W. G. Humphreys, and F. P. Guengerich, “Characterization of S-[2-(N1-adenyl)ethyl]glutathione as an adduct formed in RNA and DNA from 1,2-dibromoethane,” Chemical Research in Toxicology, vol. 3, no. 6, pp. 587–594, 1990. View at Publisher · View at Google Scholar · View at Scopus
  53. R. Thier, J. B. Taylor, S. E. Pemble et al., “Expression of mammalian glutathione S-transferase 5-5 in Salmonella typhimurium TA1535 leads to base-pair mutations upon exposure to dihalomethanes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 18, pp. 8576–8580, 1993. View at Google Scholar · View at Scopus
  54. R. A. Pegram, M. E. Andersen, S. H. Warren, T. M. Ross, and L. D. Claxton, “Glutathione S-transferase-mediated mutagenicity of trihalomethanes in Salmonella typhimurium: contrasting results with bromodichloromethane and chloroform,” Toxicology and Applied Pharmacology, vol. 144, no. 1, pp. 183–188, 1997. View at Publisher · View at Google Scholar · View at Scopus
  55. N. Ozawa and F. P. Guengerich, “Evidence for formation of an S-[2-(N7-guanyl)ethyl]glutathione adduct in glutathione-mediated binding of the carcinogen 1,2-dibromoethane to DNA,” Proceedings of the National Academy of Sciences of the United States of America, vol. 80, no. 17 I, pp. 5266–5270, 1983. View at Google Scholar · View at Scopus
  56. G. A. Marsch, R. G. Mundkowski, B. J. Morris, M. L. Manier, M. K. Hartman, and F. P. Guengerich, “Characterization of nucleoside and DNA adducts formed by S-(1-Acetoxymethyl)glutathione and implications for dihalomethane - Glutathione conjugates,” Chemical Research in Toxicology, vol. 14, no. 5, pp. 600–608, 2001. View at Publisher · View at Google Scholar · View at Scopus
  57. D. M. DeMarini, M. L. Shelton, S. H. Warren et al., “Glutathione S-transferase-mediated induction of GC → AT transitions by halomethanes in Salmonella,” Environmental and Molecular Mutagenesis, vol. 30, no. 4, pp. 440–447, 1997. View at Google Scholar
  58. S. H. Cho, E. M. Loecken, and F. P. Guengerich, “Mutagenicity of a glutathione conjugate of butadiene diepoxide,” Chemical Research in Toxicology, vol. 23, no. 10, pp. 1544–1546, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. P. J. Boogaard, S. C. J. Sumner, and J. A. Bond, “Glutathione conjugation of 1,2:3,4-Diepoxybutane in human liver and rat and mouse liver and lung in vitro,” Toxicology and Applied Pharmacology, vol. 136, no. 2, pp. 307–316, 1996. View at Publisher · View at Google Scholar · View at Scopus
  60. J. L. Nieusma, D. J. Claffey, J. A. Ruth, and D. Ross, “Stereochemical aspects of the conjugation of epoxide metabolites of butadiene with glutathione in rat liver cytosol and freshly isolated rat hepatocytes,” Toxicological Sciences, vol. 43, no. 2, pp. 102–109, 1998. View at Publisher · View at Google Scholar · View at Scopus
  61. R. Thier, S. E. Pemble, H. Kramer, J. B. Taylor, F. P. Guengerich, and B. Ketterer, “Human glutathione S-transferase T1-1 enhances mutagenicity of 1,2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium,” Carcinogenesis, vol. 17, no. 1, pp. 163–166, 1996. View at Publisher · View at Google Scholar · View at Scopus
  62. W. G. Humphreys, D. H. Kim, J. L. Cmarik, T. Shimada, and F. P. Guengerich, “Comparison of the DNA-alkylating properties and mutagenic responses of a series of S-(2-Haloethyl)-substituted cysteine and glutathione derivatives,” Biochemistry®, vol. 29, no. 45, pp. 10342–10350, 1990. View at Google Scholar · View at Scopus
  63. B. H. Monien, K. Herrmann, and S. Florian, “Metabolic activation of furfuryl alcohol: formation of 2-methylfuranyl DNA adducts in Salmonella typhimurium strains expressing human sulfotransferase 1A1 and in FVB/N mice,” Carcinogenesis, vol. 32, no. 10, pp. 1533–1539, 2011. View at Google Scholar
  64. H. Glatt, H. Boeing, C. E. H. Engelke et al., “Human cytosolic sulphotransferases: genetics, characteristics, toxicological aspects,” Mutation Research, vol. 482, no. 1-2, pp. 27–40, 2001. View at Google Scholar · View at Scopus
  65. M. Hirose, T. Yamaguchi, N. Kimoto et al., “Strong promoting activity of phenylethyl isothiocyanate and benzyl isothiocyanate on urinary bladder carcinogenesis in F344 male rats,” International Journal of Cancer, vol. 77, pp. 773–777, 1998. View at Google Scholar
  66. F. Kassie, B. Pool-Zobel, W. Parzefall, and S. Knasmüller, “Genotoxic effects of benzyl isothiocyanate, a natural chemopreventive agent,” Mutagenesis, vol. 14, no. 6, pp. 595–603, 1999. View at Google Scholar · View at Scopus
  67. L. Gamet-Payrastre, P. Li, S. Lumeau et al., “Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells,” Cancer Research, vol. 60, no. 5, pp. 1426–1433, 2000. View at Google Scholar · View at Scopus
  68. R. Thier, M. Müller, J. B. Taylor, S. E. Pemble, B. Ketterer, and F. Peter Guengerich, “Enhancement of bacterial mutagenicity of bifunctional alkylating agents by expression of mammalian glutathione S-transferase,” Chemical Research in Toxicology, vol. 8, no. 3, pp. 465–472, 1995. View at Google Scholar · View at Scopus
  69. Y. Oda, H. Yamazaki, R. Thier, B. Ketterer, F. P. Guengerich, and T. Shimada, “A new Salmonella typhimurium NM5004 strain expressing rat glutathione S-transferase 5-5: use in detection of genotoxicity of dihaloalkanes using an SOS/umu test system,” Carcinogenesis, vol. 17, no. 2, pp. 297–302, 1996. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Paolini, L. Pozzetti, P. Silingardi, C. Della Croce, G. Bronzetti, and G. Cantelli-Forti, “Isolation of a novel metabolizing system enriched in phase-II enzymes for short-term genotoxicity bioassays,” Mutation Research, vol. 413, no. 3, pp. 205–217, 1998. View at Publisher · View at Google Scholar · View at Scopus
  71. C. S. Yang and Z. Y. Wang, “Tea and cancer,” Journal of the National Cancer Institute, vol. 85, no. 13, pp. 1038–1049, 1993. View at Google Scholar · View at Scopus
  72. E. S. Fiala, G. Bobotas, and C. Kulakis, “Effects of disulfiram and related compounds on the metabolism in vivo of the colon carcinogen, 1,2-dimethylhydrazine,” Biochemical Pharmacology, vol. 26, no. 19, pp. 1763–1768, 1977. View at Publisher · View at Google Scholar · View at Scopus
  73. M. J. Wargovich, “Diallyl sulfide, a flavor component of garlic (Allium sativum), inhibits dimethylhydrazine-induced colon cancer,” Carcinogenesis, vol. 8, no. 3, pp. 487–489, 1987. View at Google Scholar · View at Scopus
  74. F. P. Guengerich and D. H. Kim, “In vitro inhibition of dihydropyridine oxidation and aflatoxin B1 activation in human liver microsomes by naringenin and other flavonoids,” Carcinogenesis, vol. 11, no. 12, pp. 2275–2279, 1990. View at Google Scholar · View at Scopus
  75. S. Langouët, D. H. Welti, N. Kerriguy et al., “Metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline in human hepatocytes: 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid is a major detoxication pathway catalyzed by cytochrome P450 1A2,” Chemical Research in Toxicology, vol. 14, no. 2, pp. 211–221, 2001. View at Publisher · View at Google Scholar · View at Scopus
  76. C. S. Yang, T. J. Smith, J. Y. Hong et al., “Cancer prevention through modulation of xenobiotic metabolising enzymes: opportunities and limitations,” The American Association for Cancer Research, vol. 37, pp. 665–666, 1996. View at Google Scholar
  77. D. W. Nebert, “Drug-metabolizing enzymes in ligand-modulated transcription,” Biochemical Pharmacology, vol. 47, no. 1, pp. 25–37, 1994. View at Publisher · View at Google Scholar · View at Scopus
  78. D. W. Nebert, “Role of genetics and drug metabolism in human cancer risk,” Mutation Research, vol. 247, no. 2, pp. 267–281, 1991. View at Publisher · View at Google Scholar · View at Scopus
  79. E. Reszka, W. Wasowicz, and J. Gromadzinska, “Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer susceptibility,” British Journal of Nutrition, vol. 96, no. 4, pp. 609–619, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. M. Paolini, A. Sapone, and F. J. Gonzalez, “Parkinson's disease, pesticides and individual vulnerability,” Trends in Pharmacological Sciences, vol. 25, no. 3, pp. 124–129, 2004. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Paolini, D. J. Nicholl, P. Bennett, O. Bandmann, and N. W. Wood, “Acetylator genotype and Parkinson's disease,” Lancet, vol. 351, no. 9096, pp. 141–142, 1998. View at Google Scholar · View at Scopus
  82. M. Paolini, G. L. Biagi, G. Cantelli-Forti et al., “Glutathione transferase polymorphism and Parkinson's disease,” Lancet, vol. 353, no. 9146, pp. 71–72, 1999. View at Google Scholar · View at Scopus
  83. M. Paolini and M. Nestle, “Pitfalls of enzyme-based molecular anticancer dietary manipulations: food for thought,” Mutation Research, vol. 543, no. 3, pp. 181–189, 2003. View at Publisher · View at Google Scholar · View at Scopus
  84. S. A. Gerrior and C. Zizza, Nutrient Content of the US Food Supply 1909–1990, US Department of Agriculture, Washington, DC, USA, 1994.
  85. A. R. Collins, B. Olmedilla, S. Southon, F. Granado, and S. J. Duthie, “Serum carotenoids and oxidative DNA damage in human lymphocytes,” Carcinogenesis, vol. 19, no. 12, pp. 2159–2162, 1998. View at Publisher · View at Google Scholar · View at Scopus
  86. M. Paolini, “Pharmaceuticals: reduce drug waste in the environment,” Nature, vol. 478, pp. 36–37, 2011. View at Google Scholar
  87. C. H. Hennekens, J. E. Buring, J. E. Manson et al., “Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease,” New England Journal of Medicine, vol. 334, no. 18, pp. 1145–1149, 1996. View at Publisher · View at Google Scholar · View at Scopus
  88. G. S. Omenn, G. E. Goodman, M. D. Thornquist et al., “Risk factors for lung cancer and for intervention effects in CARET, the beta-carotene and retinol efficacy trial,” Journal of the National Cancer Institute, vol. 88, no. 21, pp. 1550–1559, 1996. View at Publisher · View at Google Scholar · View at Scopus
  89. T. S. Hinds, W. L. West, and E. M. Knight, “Carotenoids and retinoids: a review of research, clinical, and public health applications,” Journal of Clinical Pharmacology, vol. 37, no. 7, pp. 551–558, 1997. View at Google Scholar · View at Scopus
  90. M. Paolini, S. Z. Abdel-Rahman, G. Cantelli-Forti, and M. S. Legator, “Chemoprevention or antichemoprevention? A salutary warning from the β-Carotene experience,” Journal of the National Cancer Institute, vol. 93, no. 14, pp. 1110–1111, 2001. View at Google Scholar · View at Scopus
  91. I. M. Lee, N. R. Cook, J. E. Manson, J. E. Buring, and C. H. Hennekens, “β-carotene supplementation and incidence of cancer and cardiovascular disease: the women's health study,” Journal of the National Cancer Institute, vol. 91, no. 24, pp. 2102–2106, 1999. View at Google Scholar · View at Scopus
  92. J. R. Marshall, “β-carotene: a miss for epidemiology,” Journal of the National Cancer Institute, vol. 91, no. 24, pp. 2068–2069, 1999. View at Google Scholar · View at Scopus
  93. H. Vainio, “Chemoprevention of cancer: lessons to be learned from beta-carotene trials,” Toxicology Letters, vol. 112-113, pp. 513–517, 2000. View at Publisher · View at Google Scholar · View at Scopus
  94. M. Paolini, G. Cantelli-Forti, P. Perocco, G. F. Pedulli, S. Z. Abdel-Rahman, and M. S. Legator, “Co-carcinogenic effect of β-carotene,” Nature, vol. 398, no. 6730, pp. 760–761, 1999. View at Google Scholar · View at Scopus
  95. I. D. Podmore, H. R. Griffiths, K. E. Herbert, N. Mistry, P. Mistry, and J. Lunec, “Vitamin C exhibits pro-oxidant properties,” Nature, vol. 392, no. 6676, p. 559, 1998. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Paolini, L. Pozzetti, G. F. Pedulli, E. Marchesi, and G. Cantelli-Forti, “The nature of prooxidant activity of vitamin C,” Life Sciences, vol. 64, no. 23, pp. PL273–PL278, 1999. View at Publisher · View at Google Scholar · View at Scopus
  97. S. H. Lee, T. Oe, and I. A. Blair, “Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins,” Science, vol. 292, no. 5524, pp. 2083–2086, 2001. View at Publisher · View at Google Scholar · View at Scopus