Toxic effects and intervention strategies for co-exposure to aflatoxins and fumonisins in animals and high-risk human populations
Xue, Kathy Siyu
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Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are naturally occurring mycotoxins and co-exist in many food items, particularly maize. Most studies conducted to explore toxicity, carcinogenicity, and other adverse health outcomes focused only on exposure to individual mycotoxins, and consequently did not address the issue of co-contamination and potential interactions. Recent studies in various animal models have pin-pointed to the synergistic co-carcinogenicity from co-exposure to AFB1 and FB1, and that co-contamination has also been reported in areas of high esophageal and liver cancer risks. In this dissertation studies, co-exposure to AFB1 and FB1 were evaluated in three high-risk areas for cancers, with median levels of AFB1-lysine adduct and urinary free FB1 of 1.49 pg/mg albumin and 56.92 pg/mg creatinine in Huaian, China, 62.38 pg/mg albumin and 560.73 pg/mg creatinine in Fusui, China, and 3.19 pg/mg albumin and 0.009 ng/mL in San Antonio, Texas, USA. In F344 rats that underwent sequential exposure to AFB1 and FB1, intervention with 0.5% and 1.0% UPSN clay significantly reduced GST-P+ foci counts by 77.03% (p<0.01) and 87.82% (p<0.01), and areas by 82.86% (p<0.01) and 94.29% (p<0.01), respectively, and significantly lowered the serum levels of ALP (p<0.001), ALT (p<0.05) and AST (p<0.001), as well as serum AFB1-lysine adduct (p<0.05) and urinary FB1 (p<0.01). Intervention with green tea polyphenols in a human population in Fusui County, China modulated FB1 toxicity on top of AFB1 toxicity, significantly reduced urinary FB1 by 18.95% and 33.62% (p=0.045) after 1-month treatment, and 40.18% (p=0.016) and 52.6% (p=0.0005) after 3-month treatment, in low and high dose groups, as well as urinary excretion of sphinganine (Sa), sphingosine (So), and Sa/So ratio. In a population-based case-control study conducted in Huaian, China, high-level of exposure to AFB1 and FB1 was associated with increased risk to human esophageal squamous cell carcinoma, with odds ratios of 3.689 (2.438-5.582) and 2.629 (1.711-4.041), respectively (p< 0.001 for both). Synergistic interactions of co-exposure to AFB1 and FB1 in contributing to risks of esophageal squamous cell carcinoma, and roles of potential gene-environment interactions as well as genetic polymorphisms, GSTT1 null, XPD Lys751Gln, and hOGG1 Ser326Cys, were further assessed.