Should the Focus be on Aflatoxins Alone? Ron Riley Toxicology and Mycotoxin Research Unit USDA Agricultural Research Service, Athens, Georgia To be covered: •Aflatoxin (AFB) and Fumonisin (FB) in Guatemala. •FB as a Confounder in Studies of AFB Health Effects “Sown to be eaten, it is the sacred sustenance of the men who were made of maize. Sown to make money, it means famine for the men who were made of maize” From “Men of Maize” Miguel Angel Asturias (Translation of the Popol Vuh – sacred book of the Maya) ppm n SEM All 2.6 640 0.1 16 Clean 2.6 582 0.1 273 Moldy 2.4 58 0.3 ppb n SEM All 180a 640 30 Clean 97b 582 Moldy 1011a 58 Fumonisin and Aflatoxin B1 in Guatemala in 2012 (Torres et al., unpublished) AFB1 (ppb)/Total FB (ppm) 308/4.0 195/1.3 117/1.1 200/2.3 85/2.5 70/1.8 283/1.9 13/0.3 34/2.5 16/1.4 26/1.0 105/1.0 19/1.0 30/1.7 0/1.1 8.8/4.6 2.0/2.2 10/1.4 279/2.4 12/3.8 1.1/3.8 0.4/4.6 1992- present - Disruption of sphingolipid metabolism as the mechanism of action for fumonisin-induced diseases in----•Humans? •Horse •Pig •Goat •Rabbit •Mink •Rat •Mouse •Turkey •Chicken •Duck •Catfish •Trout •Carp •Corn seedlings •Tomato The concentration of fumonisin B1 in urine and the Sa 1-P/So 1-P ratio in blood are significantly correlated in a dose-dependent manner. To be covered: •Aflatoxin (AFB) and Fumonisin (FB) in Guatemala. •FB as a Confounder in Studies of AFB Health Effects 1992- present - Disruption of sphingolipid metabolism as the mechanism of action for fumonisin-induced diseases in----•Humans •Horse •Pig •Goat •Rabbit •Mink •Rat •Mouse •Turkey •Chicken •Duck •Catfish •Trout •Carp •Corn seedlings •Tomato GSTP+ foci/or nodules Total (>5 cells/cm2) Control 0.04 AFB only 5.02 FB1 only 1.65 AFB1FB1 71.8 “…..given the interactions found experimentally, the co-contamination of crops by aflatoxins and fumonisins, and the fact that both toxins occur in populations with a high prevalence of HBV infection, a role for fumonisins in HCC is plausible.” (page 93, col 3) “Groundnuts and Mealies”Jackie Caestairs 1989) Sphingosine 1-phosphate extracellular and “Inside-Out” signaling through the G protein coupled receptors - S1PR1-5 platelets HDL S1P RBC +/- + -/- Sph S1P +/Cytoskeletal rearrangement Neurogenesis Vascular maturation + Neuronal excitation Angiogenesis Cell motility Hearing Barrier Lymphocyte integrity trafficking Sph salvage and dhSph de novo and SphK1/2 activation -/- S1P & dhS1P Traditional processing of maize in Central America Mural-Diego-Rivera-21-photo-by-Mirairi-Erdoza Financial and Administrative Support 1999 – 2012 Guatemala and Central America Red SICTA - IICA/COSUDE CONAGRAB, Comision Nacional de Granos Basicos Institute of Science and Technology Agricultural (ICTA) Consejo Nacional de Ciencia y Tecnología (CONCYT), FODECYT COMUDEB, Hospital General San Juan de Dios Puesto de Salud Santa Isabel, Escuintla Foundation for Food Nutrition for Central America and Panama (FANCAP) Institute of Nutrition of Central America and Panama (INCAP) Laboratorio Diagnóstico Molecular, CA. Pan American Health Organization United States of America USDA Foreign Agricultural Service (FAS) ILSI NA Technical Committee on Food Toxicology and Safety Assessment USDA Agricultural Research Service (ARS) National Institute of Environmental Health Sciences (US NIEHS) NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development grant (1RC4HD067971-01 )