medigraphic.com
ISSN 2395-8723 (Electronic)
ISSN 1405-888X (Print)
TIP Revista Especializada en Ciencias Químico-Biológicas

2013, Number 2

<< Back Next >>

TIP Rev Esp Cienc Quim Biol 2013; 16 (2)

Transformación de la aflatoxina B1 de alimentos, en el cancerígeno humano, aducto AFB1-ADN

Carvajal M

Language: Spanish
References: 104
Page: 109-120
PDF size: 601.27 Kb.


ABSTRACT

Aflatoxins (AF) are secondary toxic metabolites formed mainly by the molds Aspergillus flavus and A. parasiticus; they are potent mutagens and carcinogens of foods, and human exposure to them is continuous. AF bind to DNA, RNA and proteins forming AFB1-DNA adducts that accumulate for years and damage from viruses to humans. To identify and quantify the chemical reactions and molecular biology of these adducts is of primary importance because they are long-term biomarkers validated as a source of mutagenicity and risk of cancer in animals and humans. The cytochrome P450 activates AF as an unstable molecule called 8,9 AFB1 epoxide, that binds mainly to the N7 of the guanine nucleotide forming adducts that are the active carcinogens themselves and, as biomarkers, an objective measure of human exposure to environmental carcinogens. Adducts represent an integration of exposure, absorption, distribution, metabolism, DNA repair, and cell turnover. The different issues presented here are the formation of AFB1-DNA adducts, in vitro and in vivo studies, dietary AFB1 exposure, effects, development of human cancer and mutations in the p53 tumor suppressor gene, the effect of diet, routes of exposure, vitamins, kinds of AFB1-DNA adducts, methodology used for their study and their control.


REFERENCES

  1. Asao, T. et al. Aflatoxins B and G. J. Am. Chem. Soc. 85, 1706- 1707 (1963).

  2. Butler, W.H. Aflatoxins in Mycotoxins (ed. Purchase, I.F.H.) 1-28 (Elsevier, Amsterdam, 1974).

  3. Diener, U.L. & Davis, N.D. in Aflatoxin in Maize: A proceedings of the Workshop (eds. Zuber, M.S., Lillehoj, E.B. & Renfro, B.L.) 298-307 (CYMMYT/UNDP/USDA, El Batán, México, D.F., 1986).

  4. OPS-OMS. Micotoxinas. Criterios de la salud ambiental 11: Micotoxinas (Organización Mundial de la Salud, Publicación Científica 453, Washington, USA, 1983).

  5. Manonmani, H.K., Anand, S., Chandrashekar, A. & Rati, E.R. Detection of aflatoxigenic fungi in selected food commodities by PCR. Process Biochem. 40, 2859-2864 (2005).

  6. Chang, S.B., Abdel-Kader, M.M., Wick, E.L. & Wogan, G.N. Aflatoxin B2: Chemical identity and biological activity. Science 142, 1191-1192 (1963).

  7. Soriano del Castillo, J.M. et al. Micotoxinas en alimentos (Ediciones Díaz de Santos, España, 2007). pp: 3-16, 167-170

  8. Price, R.L. & Jorgensen, K.V. Effects of processing on aflatoxins levels and on mutagenic potential of tortillas made from naturally contaminated corn. J. Food Sci. 50, 347-349 (1985).

  9. Sweeney, M.J. & Dobson, A.D.W. Molecular biology of mycotoxin biosynthesis. FEMS Microbiol. Lett. 175, 149-163 (1999).

  10. Eaton, D.I., Ramsdell, H.S., & Neal, G.E. in The toxicology of aflatoxins. Human Health, Veterinary and Agricultural Significance (ed. Eaton, D.L. & Groopman J.J.) 45-72 (Academic Press, Inc., San Diego, USA, 1994).

  11. Wyllie, T.D. & Morehouse, L.G. Mycotoxin Fungi, Mycotoxins, Mycotoxicoses. An Encyclopedic Handboook 3 (Mercel Dekker, Inc., New York, USA,1978).

  12. Olsen, J.H., Dragsted, I. & Autrup, H. Cancer risk and occupational exposure to aflatoxins in Denmark. Br. J. Cancer 58, 236-250 (1988).

  13. Reye, R.D.K., Morgan, G. & Baral, J. Encephalopathy and fatty degeneration of the viscera: A disease entity in childhood. Lancet 2, 749-752 (1963).

  14. Apeagyei, F., Lamplugh, S.M., Hendrickse, R.G., Afframy, K. & Lucas, S. Aflatoxins in the liver of children with kwashiorkor in Ghana. Trop.Geogr. Med. Home 9-12 (1982).

  15. Jeffrey, A.M. & Williams, G.M. Risk assessment of DNA-reactive carcinogens in food. Toxicol. Appl. Pharmacol.207, S628-S635 (2005).

  16. Wogan, G.N. Aflatoxins as risk factors for primary hepatocellular carcinoma in humans (Pennington Center Nutrition Series, Louisiana St., USA, 1991).

  17. Krishnamachari, K.A., Bhat, R.V., Naragajan, V. & Tilak, T.B. Hepatitis due to aflatoxicosis. An outbreak in Western India. Lancet 1, 1061-1063 (1975).

  18. Sornmayura, P. et al. Dysplastic nodules and small primary carcinoma of the liver: A study detecting the early morphological changes during hepatocarcinogenesis. J. Med. Assoc. Thailand 90, 352-362 (2007).

  19. Groopman, J.D. et al. Molecular dosimetry of urinary aflatoxin- DNA adducts in people living in Guangxi autonomous region, People's Republic of China. Cancer Res. 52, 45-52 (1992).

  20. Lewis, L. et al. Aflatoxin contamination of commercial maize products during an outbreak of acute aflatoxicosis in eastern and central Kenya. Environ. Health Persp. 113, 1763-1767 (2005).

  21. Phillips, J.C., Davies, S. & Lake, B.G. Dose-response relationships for hepatic aflatoxin B1-DNA adduct formation in the rat in vivo and in vitro: the use of immunoslot blotting for adduct quantitation. Teratog. Carcinog. Mutagen.19, 157-170 (1999).

  22. Donnelly, P.J. et al. Biotransformation of aflatoxin B1 in human lung.Carcinogenesis 17, 2487-2494 (1996).

  23. Bronson, R., Birt, D. & Meydani, S.N. Biomarkers as early predictors of long-term health status and human immune function. Nutr. Rev. 57, S7-S12 (1999).

  24. Essigmann, J.M., Croy, R.G., Bennett, R.A. & Wogan, G.N. Metabolic activation of aflatoxin B1: Patterns of DNA adduct formation, removal, and excretion in relation to carcinogenesis. Drug Metab.Rev. 13, 581-602 (1982).

  25. Jacobsen, J.S., Refolo, L.M., Conley, M.P., Sambamurti, K. & Humayun, M.Z. DNA replication-blocking properties of adducts formed by aflatoxin B1-2,3-dichloride and aflatoxin B1-2,3-oxide. Mutat Res. 179, 89-101 (1987).

  26. Ross, M.K., Said, B. & Shank, R.C. DNA-damaging effects of genotoxins in mixture: modulation of covalent binding to DNA. Toxicol. Sci. 53, 224-236 (2000).

  27. Ames, B.N. Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Sciences 221, 1256-1264 (1983).

  28. Shupe, T. & Sell, S. Low hepatic glutathione S-transferase and increased hepatic DNA adduction contribute to increased tumorigenicity of Aflatoxin B1 in newborn and partially hepatectomized mice. Toxicol. Lett. 148, 1-9 (2004).

  29. Essigmann, J.M. et al. Structural Identification of the major DNA adduct formed by Aflatoxin B1 in vitro. Proc. Natl. Acad. Sci. USA 74, 1870-1874 (1977).

  30. Yu, F.L., Huang, J.X., Bender, W., Wu, Z. & Chang, J.C.S. Evidence for the covalent binding of aflatoxin B1-dichloride to cytosine in DNA. Carcinogenesis 12, 997-1002 (1991).

  31. Chelcheleh, M. & Allameh, A. In vivo biotransformation of AFB1 and its interaction with cellular macromolecules in neonatal rats. Mech. Ageing Dev. 78, 189-196 (1995).

  32. Fujimoto, Y., Hampton, L.L., Luo, L.D., Wirth, P.J. & Thorgeirsson, S.S. Low frequency of p53 gene mutation in tumors induced by AFB1 in nonhuman primates. Cancer Res. 52, 1044-1046 (1992).

  33. Hsieh, D.P.H. & Atkinson, D.N. Recent aflatoxin exposure and mutation at codon 249 of the human p53 gene: lack of association. Food Addit. Contam. 12, 421-424 (1995).

  34. Irvin, T.R. & Wogan, G.N. Quantitation of AFB1 adduction within the ribosomal RNA gene sequences of rat liver DNA. Proc. Natl. Acad. Sci. USA 81, 664-668 (1984).

  35. Lin, J.K., Miller, J.A. & Miller, E.C. 2,3-dihydro-2-(guan-7-yl)- 3-hydroxy-aflatoxin B1, a major acid hydrolysis product of AFB1-DNA or ribosomal RNA adducts formed in hepatic microsome-mediated reactions and in rat liver in vivo. Cancer Res. 37, 4430-4438 (1977).

  36. Benasutti, M., Ejadi, S., Whitlow, M.D. & Loechler, E.L. Mapping the binding site of Aflatoxin B1 in DNA: Systematic analysis of the reactivity of Aflatoxin B1 with guanines in different DNA sequences. Biochemistry 27, 472-481 (1988).

  37. Shaulsky, G., Johnson, R.L., Shockcor, J.P., Taylor, L.C.E. & Stark, A.A. Properties of aflatoxin-DNA adducts formed by photoactivation and characterization of the major photoadduct as aflatoxin-N7-guanine. Carcinogenesis 11, 519-527 (1990).

  38. Troxel, C.M., Buhler, D.R., Hendricks, J.D. & Bailey, G.S. CYP1A induction by β-naphtho flavone, Aroclor 1254 and 2,3,7,8-tetrachlorodibenzo-p-dioxin and its influence on AFB1 metabolism and DNA adduction in zebrafish (Danio rerio). Toxicol. Appl. Pharmacol. 146, 69-78 (1997).

  39. Autrup, H. & Wakhisi, J. in Methods for detecting DNA damaging agents in humans: applications in cancer epidemiology and prevention (eds. Bartsch, H., Hemminki, K. & O´Neill, I.K.) 63-66 (International Agency for Research on Cancer, Scientific Publications No. 89, Lyon, France, 1988).

  40. Gopalakrishnan, S., Harris, T.M. & Stone, M.P. Intercalation of aflatoxin B1 in two oligodeoxynucleotide adducts: comparative 1H NMR analysis of d(ATCAFBGAT), d(ATCGAT) and d(ATAFBGCAT)2. Biochemistry 29, 10438-10448 (1990).

  41. Croy, R.G. & Wogan, G.N. Identification of an AFP1-DNA adduct formed in vivo in rat liver. Proc. Am. Assoc. Cancer Res. 20, 182 (1979).

  42. Schoenhard, G.L. et al. Aflatoxicol-induced hepatocellular carcinoma in rainbow trout (Salmo gairdneri) and the synergistic effects of cyclopropenoid fatty acids. Cancer Res. 41, 1011-1014 (1981).

  43. Loveland, P.M.et al. AFB1 and aflatoxicol metabolism in rainbow trout (Salmo gairdneri) and the effects of dietary cyclopropene. J. Environ. Pathol. Toxicol. 2, 707-718 (1979).

  44. Bailey, G.S. et al. Quantitative carcinogenesis and dosimetry in rainbow trout for AFB1 and aflatoxicol, two aflatoxins that form the same DNA adduct. Mutat. Res. 313, 25-38 (1994).

  45. Martin, C.N. & Garner, R.C. Aflatoxin-B oxide generated by chemical or enzymatic oxidation of AFB1 causes guanine substitution in nucleic acids. Nature 267, 863-865 (1977).

  46. Croy, R.G. & Wogan, G.N. Temporal patterns of covalent DNA adducts in rat liver after single and multiple doses of aflatoxin B1. Cancer Res. 41, 197-203 (1981).

  47. Lee, H.S., Sarosi, I. & Vyas, G.N. Aflatoxin B1 formamido pyrimidine adducts in human hepatocarcinogenesis: a preliminary report. Gastroenterology 97, 1281-1287 (1989).

  48. Dashwood, R.H. et al. in Handbook of Applied Mycology. Mycotoxins in Ecological Systems Vol. 5 (eds. Bhatnagar, D., Lillehoj, E.B. & Arora, D.K.) 183-211 (Marcel Dekker, Inc., New York, USA, 1992).

  49. Osterman-Golkar, S., Ehrenberg, L., Segerbäck, D. & Hallstrom, I. Evaluation of the genetic risks of alkylating agents. Mutat. Res. 34, 1-10 (1976).

  50. Segerbäck, D., Calleman, C.J., Ehrenberg, L., Lofröth, G. & Osterman-Golkar, S. Evaluation of genetic risks of alkylating agents. IV Quantitative determination of alkylating aminoacids in hemoglobin as measure of the dose after treatment of mice with methyl methanesulfonate. Mutat. Res. 49, 71-82 (1978).

  51. Turner, P.C., Dingley, K.H., Coxhead, J., Russell, S. & Garner, C.R. Detectable levels of serum AFB1-albumin adducts in the United Kingdom population: implications for AFB1 exposure in the United Kingdom. Cancer Epidemiol. Biomark. Prev. 7, 441-447 (1998).

  52. Wang, J.S. et al. Development of Aflatoxin B1-lysine adduct monoclonal antibody for human exposure studies. Applied & Environ. Microbiol. 67, 2712-2717 (2001).

  53. Wild, C.P. et al. Aflatoxin-albumin adducts: a basis for comparative carcinogenesis between animals and humans. Cancer Epidemiol. Biomark. Prev. 5, 179-189 (1996).

  54. Anwar, W.A., Khalil, M.M. & Wild, C.P. Micronuclei, chromosomal aberrations and AF-albumin adducts in experimental animals after exposure to AFB1. Mutat. Res. 322, 61-67 (1994).

  55. D´Andrea, A.D. & Hasseltine, W.A. Modification of DNA by AFB1 creates alkali-labile lesions in DNA at positions of guanine and adenine. Proc. Natl. Acad. Sci. USA 75, 4120-4124 (1978).

  56. Hasler, J.A., Dube, N., Nyathi, C.B., Fuhrmann, H. & Sallmann, H.P. The influence of dietary fat on hepatic bioactivation of AFB1 in rats. Res. Commun. Chem. Pathol. Pharmacol. 83, 279-287 (1994).

  57. Schrager, T.F., Newberne, P.M., Pikul, A.H. & Groopman, J.D. Aflatoxin-DNA adduct formation in chronically dosed rats fed a choline-deficient diet. Carcinogenesis 11,177-180 (1990).

  58. Chou, M.W. & Chen, W. Food restriction reduces Aflatoxin B1 (AFB1)-DNA adduct formation, AFB1-glutathione conjugation and DNA damage in AFB1-treated male F344 rats and B6C3F1 mice. J. Nutr. 127, 210-217 (1997).

  59. Chou, M.W., Shaddock, J.G., Kong, J., Hart, R.W. & Casciano, D.A. Effect of dietary restriction on partial hepatectomy-induced liver regeneration of aged F344 rats. Cancer Lett. 91, 191-197 (1995).

  60. Gao, P. & Chou, M.W. Effect of caloric restriction on hepatic nuclear DNA damage in male Fischer 344 rats treated with Aflatoxin B1. Toxicol. Lett. 61, 233-242 (1992).

  61. Liu, L. & Massey, T.E. Bioactivation of AFB1 by lipoxygenases, prostaglandin H synthase and cytochrome P450 monooxygenase in guinea-pig tissues. Carcinogenesis 13, 533-539 (1992).

  62. Yu, M.W., Chiang, Y.C., Lien, J.P. & Chen, C.J. Plasma antioxidant vitamins, chronic hepatitis B virus infection and urinary AFB1- DNA adducts in healthy males. Carcinogenesis 18, 1189-1194 (1997).

  63. Gradelet, S., Le Bon, A.M., Berges, R., Suschetet, M. & Astorg, P. Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DNA damage in the rat: role of the modulation of AFB1 metabolism. Carcinogenesis 19, 403-411 (1998).

  64. Reddy, L., Odhav, B. & Bhoola, K. AFB1-induced toxicity in HepG2 cells inhibited by carotenoids: morphology, apoptosis and DNA damage. Biol. Chem. 387, 87-93 (2006).

  65. Zarba, A., Hmieleski, R., Hemenway, D.R., Jakab, G.J. & Groopman, J.D. Aflatoxin B1-DNA adduct formation in rat liver following exposure by aerosol inhalation. Carcinogenesis 13, 1031-1033 (1992).

  66. Biswas, G. et al. Comparative kinetic studies on aflatoxin B1 binding to pulmonary and hepatic DNA of rat and hamster receiving the carcinogen intratracheally. Teratog. Carcinog. Mutagen. 13, 259-268 (1993).

  67. Putt, D.A., Ding, X., Coon, M.J. & Hollenberg, P.F. Metabolism of aflatoxin B1 by rabbit and rat nasal mucosa microsomes and purified cytochrome P450, including isoforms 2A10 and 2A11. Carcinogenesis 16, 1411-1417 (1995).

  68. Harrison, J.C., Carvajal, M. & Garner, R.C. in Human Carcinogen Exposure. Biomonitoring and Risk Assessment (eds. Garner, R.C., Farmer, P.B., Stell, G.T. & Wright, A.S.) 255-265 (IRL Press, Oxford University Press, 1991).

  69. Sotomayor, R.E. et al. Effects of intermittent exposure to AFB1 on DNA and RNA adduct formation in rat liver: Dose-response and temporal patterns. Toxicol. Sci. 73, 329-338 (2003).

  70. Walton, M. et al. Liquid chromatography electrospray-mass spectrometry of urinary AF biomarkers: characterization and application to dosimetry and chemoprevention in rats. Chem. Res. Toxicol. 14, 919-926 (2001).

  71. Towner, R.A., Qian, S.Y., Kadiiska, M.B. & Mason, R.P. In vivo identification of aflatoxin-induced free radicals in rat bile. Free Radic. Biol. Med. 35,1330-1340 (2003).

  72. Hsieh, L.L., Hsu, S.W., Chen, D.S. & Santella, R.M. Immunological detection of AFB1-DNA adducts formed in vivo. Cancer Res. 48, 6328-6331 (1988).

  73. 73.Zhang,Y.J. et al. Quantitation of AFB1-DNA adducts in woodchuck hepatocytes and rat liver tissue by indirect immunofluorescence analysis. Cancer Res. 51, 1720-1725 (1991).

  74. Choi, M.J., Lee, J.W. & Lee, B.M. Comparative assessment of DNA adduct formation, Salmonella mutagenicity, and chromosome aberration assays as short-term tests for DNA damage. J. Toxicol. Environ. Health. 49, 271-284 (1996).

  75. Mandal, S. et al. Inhibition of aflatoxin B1 mutagenesis in Salmonella typhimurium and DNA damage in cultured rat and human tracheobronchial tissues by ellagic acid. Carcinogenesis 8, 1651-1656 (1987).

  76. Denissenko, M.F., Cahill, J., Koudriakova, T.B., Gerber, N. & Pfeifer, G.P. Quantitation and mapping of AFB1-induced DNA damage in genomic DNA using AFB1-8,9-epoxide and microsomal activation systems. Mutat. Res. 425, 205-211 (1999).

  77. Loury, D.N. & Hsieh, D.P. Effects of chronic exposure to AFB1 and AFM1 on the in vivo covalent binding of AFB1 to hepatic macromolecules. J. Toxicol. Environ. Health 13, 575-587 (1984).

  78. Knight, L.P., Primiano, T., Groopman, J.D., Kensler, T.W. & Sutter, T.R. cDNA cloning, expression and activity of a second human AFB1-metabolizing member of the aldo-keto reductase superfamily, AKR7A3. Carcinogenesis20, 1215-1223 (1999).

  79. Urban, J.D. et al. Functional selectivity and classical concepts of quantitative pharmacology. J. Pharmacol. Exp. Ther. 320, 1-13 (2007).

  80. Takahashi, N., Harttig, U., Williams, D.E. & Bailey, G.S. The model Ah-receptor agonist ß-naphthoflavone inhibits aflatoxin B1-DNA binding in vivo in rainbow trout at dietary levels that do not induce CYP1A enzymes. Carcinogenesis 17, 79-87 (1996).

  81. Im, S.H., Bolt, M.W., Stewart, R.K. & Massey, T.E. Modulation of AFB1 biotransformation by ß-naphthoflavone in isolated rabbit lung cells. Arch. Toxicol. 71, 72-79 (1996).

  82. Pelkonen, P., Lang, M.A., Negishi, M., Wild, C.P. & Juvonen, R.O. Interaction of AFB1 with cytochrome P450 2A5 and its mutants: correlation with metabolic activation and toxicity. Chem. Res. Toxicol. 10, 85-90 (1997).

  83. Pelkonen, P., Lang, M., Wild, C.P., Negishi, M. & Juvonen, R.O. Activation of AFB1 by mouse CYP2A enzymes and cytotoxicity in recombinant yeast cells. Eur. J. Pharmacol. 292, 67-73 (1994).

  84. Hayes, J.D., Judah, D.J. & Neal, G.E. Resistance to AFB1 is associated with the expression of a novel aldo-keto reductase which has catalytic activity towards a cytotoxic aldehydecontaining metabolite of the toxin. Cancer Res. 53, 3887-3894 (1993).

  85. Tamimi, R.M., Lagiou, P., Adami, H.O. & Trichopoulos, D. Prospects for chemoprevention of cancer. J. Intern. Med. 251, 286-300 (2002).

  86. Egner, P.A., De Matos, P., Groopman, J.D. & Kensler, T.W. Effect of 1,2-dithiole-3-thione, a monofunctional enzyme inducer, on Aflatoxin-DNA adduct formation in rat liver. Proc. Annual Meeting of the Am. Assoc. Canc. Res. 31, 119 (1990).

  87. Allameh, A. Comparison of the effect of low- and high-dose dietary butylated hydroxy toluene on microsome-mediated AFB1-DNA binding. Cancer Lett. 114, 217-220 (1997).

  88. Salocks, C.B., Hsieh, D.P. & Byard, J.L. Effects of butylated hydroxytoluene pretreatment on the metabolism and genotoxicity of AFB1 in primary cultures of adult rat hepatocytes: selective reduction of nucleic acid binding. Toxicol. Appl. Pharmacol. 76, 498-509 (1984).

  89. Shi, C.Y., Chua, S.C., Lee, H.P. & Ong, C.N. Inhibition of AFB1- DNA binding and adduct formation by selenium in rats. Cancer Lett. 29, 203-208 (1994).

  90. Benson, A.B. Oltipraz: a laboratory and clinical review. J. Cell. Biochem. Suppl. 17F, 278-291 (1993).

  91. Salbe, A.D. & Bjeldanes, L.F. Effect of diet and route of administration on the DNA binding of AFB1 in the rat. Carcinogenesis 10, 629-634 (1989).

  92. Stresser, D.M., Williams, D.E., McLellan, L.I., Harris, T.M. & Bailey, G.S. Indole-3-carbinol induces a rat liver glutathione transferase subunit (Yc2) with high activity toward AFB1 exoepoxide. Association with reduced levels of hepatic AF-DNA adducts in vivo. Drug Metab. Dispos. 22, 392-399 (1994).

  93. Kensler, T.W. et al. Effects of glucosinolate-rich broccoli sprouts on urinary levels of AF-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo Township, Qidong, People's Republic of China. Cancer Epidemiol. Biomarkers Prev. 14, 2605-2613 (2005).

  94. Kensler, T.W. Chemoprevention by inducers of carcinogen detoxication enzymes. Environ. Health Perspect. 105 Suppl, 965-970 (1997).

  95. Bolton, M.G. et al. Transient intervention with oltipraz protects against aflatoxin-induced hepatic tumorigenesis. Cancer Res. 53, 3499-3504 (1993).

  96. O'Dwyer, P.J. et al. Modulation of gene expression in subjects at risk for colorectal cancer by the chemopreventive dithiolethione Oltipraz. J. Clin. Investig. 98, 1210-1217 (1996).

  97. Kelly, V.P. et al. Chemoprevention of AFB1 hepatocarcinogenesis by coumarin, a natural benzopyrone that is a potent inducer of AFB1-aldehyde reductase, the glutathione S-transferase A5 and P1 subunits, and NAD(P)H: quinone oxidoreductase in rat liver. Cancer Res. 60, 957-969 (2000).

  98. Cavin, C., Holzhauser, D., Constable, A., Huggett, A.C. & Schilter, B. The coffee-specific diterpenes cafestol and kahweol protect against AFB1-induced genotoxicity through a dual mechanism. Carcinogenesis 19, 1369-1375 (1998).

  99. Elegbede, J.A. & Gould, M.N. Monoterpenes reduced adducts formation in rats exposed to AFB1. African J. Biotech. Acad. J. 1, 46-49 (2002).

  100. Miyata, M., Takano, H., Guo, L.Q., Nagata, K. & Yamazoe, Y. Grapefruit juice intake does not enhance but rather protects against AFB1-induced liver DNA damage through a reduction in hepatic CYP3A activity. Carcinogenesis25, 203-209 (2004).

  101. Netke, S.P., Roomi, M.W., Tsao, C. & Niedzwiecki, A. Ascorbic acid protects guinea pigs from acute aflatoxin toxicity. Toxicol. Appl. Pharmacol. 143, 429-435 (1997).

  102. Wong, B.Y., Lau, B.H., Yamasaki, T. & Teel, R.W. Inhibition of dexamethasone-induced cytochrome P450-mediated mutagenicity and metabolism of AFB1 by Chinese medicinal herbs. Eur. J. Cancer Prev. 2, 351-356 (1993).

  103. Egner, P.A. et al. Chlorophyllin intervention reduces AF-DNA adducts in individuals at high risk for liver cancer. Proc. Natl. Acad. Sci. USA 98, 14601-14606 (2001).

  104. El-Nezami, H.S. et al. Probiotic supplementation reduces a biomarker for increased risk of liver cancer in young men from Southern China. Am. J. Clin. Nutr., Amer. Soc. Clin. Nut. 83, 1199-1203 (2006).




2020     |     www.medigraphic.com