The risk of developing hepatocellular carcinoma (HCC), a leading cause of death in humans infected with hepatitis virus (HV), is significantly enhanced by dietary exposure to aflatoxin (AF). Also, the carcinogenicity of AF can be "promoted" with exposure to fumonisin (FB), a common co-contaminant with AF. Importantly, a significant increase in HCC in Texas has been documented in multiple regions of the San Antonio metropolitan area of Bexar County. In a pilot study, we have shown this population is at risk for AF/FB exposure due to the intake of contaminated foods. Thus, innovative strategies for the prevention of HV/AF/FB-induced HCC are high priorities. We have developed a novel approach using a smectite clay (NS) that selectively sorbs AF and FB in the GI tract. In clinical trials in Texas and Ghana, we confirmed the safety and efficacy of NS. In the proposed project, our aims are based on the central hypothesis that intervention with NS will decrease AF/FB exposure in study participants in Bexar County. Our objectives focus on confirming the molecular mechanisms of refined NS and investigating its ability to diminish the incidence of preneoplastic hepatic lesions in a rodent model. Also, biomarkers of toxin exposure will be measured in samples from participants following a 3-month clinical trial. We postulate that this agent will reduce primary exposure to AF/FB and, in turn, reduce the incidence of HCC in vulnerable commumnities in Texas. Between 2002 and 2006, the incidence of HCV infection and HCC in populations in Bexar County was significantly higher compared to other counties in Texas. Therefore, in these populations at risk for HCC, it is desirable to decrease dietary exposure to AF/FB. Mitigating AF/FB exposure using a toxin enterosorbent (i.e., NS clay) represents an innovative, practical, sustainable and environmentally benign approach. Moreover, this strategy is "ground-breaking" in that a refined smectite clay can be used to decrease the bioavailability of a potent cancer initiator (AF) as well as a potent cancer promoter (FB) by preferentially and tightly sequestering both toxins from the GI tract. The preferred delivery of a therapeutic dose of NS clay may eventually be through its inclusion in common foods such as peanut butter, corn meal, tortillas, or salt (like iodine).

Public Health Relevance

The findings from this research will be of direct relevance to underserved metropolitan, rural and border communities in Texas where the incidence of liver disease is elevated in the poor who are frequently infected with HV and exposed to dietary AF/FB. The long-term goal is to provide an intervention that will improve liver disease management in high risk populations by reducing exposure to AF and FB.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Research Project (R01)
Project #
5R01MD005819-03
Application #
8288643
Study Section
Special Emphasis Panel (ZMD1-PA (05))
Program Officer
Rajapakse, Nishadi
Project Start
2010-09-30
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$329,746
Indirect Cost
$40,085
Name
Texas A&M University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
078592789
City
College Station
State
TX
Country
United States
Zip Code
77845
Mitchell, Nicole J; Xue, Kathy S; Lin, Shuhan et al. (2014) Calcium montmorillonite clay reduces AFB1 and FB1 biomarkers in rats exposed to single and co-exposures of aflatoxin and fumonisin. J Appl Toxicol 34:795-804
Elmore, Sarah E; Mitchell, Nicole; Mays, Travis et al. (2014) Common African cooking processes do not affect the aflatoxin binding efficacy of refined calcium montmorillonite clay. Food Control 37:
Qian, Guoqing; Tang, Lili; Guo, Xia et al. (2014) Aflatoxin B1 modulates the expression of phenotypic markers and cytokines by splenic lymphocytes of male F344 rats. J Appl Toxicol 34:241-9
Qian, Guoqing; Tang, Lili; Wang, Franklin et al. (2013) Physiologically based toxicokinetics of serum aflatoxin B1-lysine adduct in F344 rats. Toxicology 303:147-51
Qian, Guoqing; Wang, Franklin; Tang, Lili et al. (2013) Integrative toxicopathological evaluation of aflatoxin Býýý exposure in F344 rats. Toxicol Pathol 41:1093-105
Mitchell, Nicole J; Kumi, Justice; Johnson, Natalie M et al. (2013) Reduction in the urinary aflatoxin M1 biomarker as an early indicator of the efficacy of dietary interventions to reduce exposure to aflatoxins. Biomarkers 18:391-8
Robinson, A; Johnson, N M; Strey, A et al. (2012) Calcium montmorillonite clay reduces urinary biomarkers of fumonisin Býýý exposure in rats and humans. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 29:809-18