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Global Aflatoxin Exposure in Various Human Populations

Global Aflatoxin Exposure in Various Human Populations. J.-S. Wang, J. H. Williams, and T. D. Phillips University of Georgia Texas A & M University. Problem Statement. Aflatoxins represent a group of potent mycotoxins; Produced mainly by Aspergillus flavus and A. parasiticus;

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Global Aflatoxin Exposure in Various Human Populations

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  1. Global Aflatoxin Exposure in Various Human Populations J.-S. Wang, J. H. Williams, and T. D. Phillips University of Georgia Texas A & M University

  2. Problem Statement • Aflatoxins represent a group of potent mycotoxins; • Produced mainly by Aspergillus flavus and A. parasiticus; • Widespread food contaminants, especially for corn and corn products, groundnuts, and rice; • Serious public health and food safety problems in developing countries, even in developed countries; • Human aflatoxicosis and hepatocellular carcinoma; • Immunosuppressors; • Anti-nutritional agents (inhibition of growth and development in children).

  3. Research Goals • To establish a biomarker based global network for assessment of AF exposure in high-risk human populations; • To link AF exposure with nutritional deficiency, growth inhibition, and infectious diseases; • To investigate the efficacy of intervention strategies for diminishing incidence and mortality from human aflatoxicosis and other diseases.

  4. Biomarkers Altered Structure/ Function Internal Dose Biologically Effective Dose Early Biological Effect Chronic Disease Exposure Susceptibility markers Interventions Exposure biomarkers Effect biomarkers

  5. Metabolic Pathways of AFB1 P-450 1A2 P-450 AFM1 AFB1 Other metabolites (Milk & urine) AFM1-8,9-epoxide Phase I P-450 1A2, 3A4 AFB1-8,9-epoxide DNA adducts (tissue & urine) Phase II GSTs +H2O AFB1-diol Albumin adducts AFB-NAC (blood) (urine)

  6. Working Hypothesis Levels of AFB1-albumin adduct in human serum are highly stable and related to long-term aflatoxin exposure and will be a reliable exposure biomarker as well as an effective biological response indicator for aflatoxin-related human diseases in high-risk populations.

  7. Method • Procedures include pronase digestion, solid-phase concentration and purification, HPLC-fluorescent detection, and MS confirmation; • Limit of detection: 0.1 pg/mL serum or 10 fg/mg albumin; • Recovery: 75-90% for various spiked concentrations; • Reproducibility and accuracy: excellent.

  8. Sources of Samples • Serum samples from the San Antonio Environmental Health Study; • Serum samples from the case-control study, Guangxi, China; • Serum samples from Ghanaian adults and infants; • Serum samples from Burkina Faso human populations; • Serum samples from Malaysia; • Serum samples from Haitians; • Serum samples from two cohort studies in Uganda.

  9. Europe North America Asia Africa Latin America Oceania Burkina Faso China USA Ghana Pakistan Haiti Uganda Malaysia

  10. San Antonio Samples

  11. Guangxi Case Samples

  12. Guangxi Control Samples

  13. Ghanaian Adult Samples

  14. Ghanaian Infant Samples

  15. Burkina Faso Samples

  16. Haitian Samples

  17. Malaysia Samples

  18. Levels of AFB1-lysine adducts (pg/mg albumin) in human serum samples

  19. Levels of AFB1-lysine adducts (pg/mg albumin) in human serum samples

  20. Levels of AFB1-Lysine Adduct in Human Serum Samples

  21. Levels of AFB1-Lysine Adduct in Uganda General Population Cohort Samples

  22. Levels of AFB-Lysine Adducts (pg/mg Albumin) in General Population Cohort, Uganda

  23. Levels of AFB1-Lysine Adduct in Uganda RAIKAI Cohort Serum Samples

  24. Levels of AFB1-Lysine Adduct in Uganda RAIKAI Cohort Serum Samples

  25. Summary • Ubiquitous aflatoxin exposure was found in human populations of developing nations, as compared to the US population; • Greater variability in aflatoxin exposure levels was found: West African countries > Southeast Asian countries > East African countris > Caribbean countries > USA; • Aflatoxin exposure levels are associated with aflatoxin-related human diseases; • Intervention strategies need to be implemented in high exposed human populations.

  26. Acknowledgements • Worldwide research collaborators; • Research grant: 1RO1MD005819 from NIH/NIMHHD; • Research Agreement ECG-A-00-0700001-00 from:

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