260 likes | 401 Views
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;
E N D
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; • 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).
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.
Biomarkers Altered Structure/ Function Internal Dose Biologically Effective Dose Early Biological Effect Chronic Disease Exposure Susceptibility markers Interventions Exposure biomarkers Effect biomarkers
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)
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.
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.
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.
Europe North America Asia Africa Latin America Oceania Burkina Faso China USA Ghana Pakistan Haiti Uganda Malaysia
Levels of AFB1-lysine adducts (pg/mg albumin) in human serum samples
Levels of AFB1-lysine adducts (pg/mg albumin) in human serum samples
Levels of AFB1-Lysine Adduct in Uganda General Population Cohort Samples
Levels of AFB-Lysine Adducts (pg/mg Albumin) in General Population Cohort, Uganda
Levels of AFB1-Lysine Adduct in Uganda RAIKAI Cohort Serum Samples
Levels of AFB1-Lysine Adduct in Uganda RAIKAI Cohort Serum Samples
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.
Acknowledgements • Worldwide research collaborators; • Research grant: 1RO1MD005819 from NIH/NIMHHD; • Research Agreement ECG-A-00-0700001-00 from: