The goals of this Project are to incorporate the use of biomarkers into primary and secondary (chemoprevention) interventions in high risk populations exposed to aflatoxins. In all preventive interventions there must be objective metrics with which to quantify success. Subsequently, the cost-benefit balance of the intervention can be analyzed and appropriately targeted toward high risk subgroups or individuals within a population. One of the tenets of the molecular epidemiology paradigm is that a mechanistic understanding of the actions of carcinogens can lead to novel prevention technologies. Therefore, the aims of this Project are 3-fold. First, it is to improve existent liquid chromatography-electrospray ionization tandem mass spectroscopy (LC-ESI-MS/MS) methodology for quantitative analysis of major urinary aflatoxin metabolites (e.g., aflatoxin-N7-guanine, aflatoxin M1, aflatoxin P1, aflatoxin-mercapturic acid). Second, it is to determine the impact of primary prevention strategies in West Africa using targeted contamination reduction strategies in community settings. The investigators will develop interventions aimed at: (1) mothers and young children during the weaning period when mycotoxin-contaminated maize-based foods are first introduced into the child?s diet; and (2) local subsistence farmers attempting to reduce contamination of their dietary staple crops, groundnuts and maize. Aflatoxin and fumonisin biomarkers will be used as outcome measures, while in part (1) the investigators will also examine the effects of intervention on child growth and immune parameters. Third, it is to follow up initial results of the investigators' chlorophyllin intervention where they demonstrated a significantly reduced excretion of aflatoxin-N7-guanine at 3 months by examining the impact of the intervention on biomarker modulation at additional time points. They will also analyze urine samples collected during the course of a one-year long intervention with oltipraz in Qidong for magnitude and persistence of modulatory effects on DNA adduct and other aflatoxin biomarkers. It is the hypothesis that levels of biomarkers for the biologically effective dose of carcinogens will be predictive of the efficacy of primary and chemopreventive interventions.
The specific aims of this Project have been designed to translate the biomarkers developed and validated in Projects 1 and 4 into metrics to determine the impact of the interventions in high risk populations.
|Chen, Taoyang; Qian, Gengsun; Fan, Chunsun et al. (2018) Qidong hepatitis B virus infection cohort: a 25-year prospective study in high risk area of primary liver cancer. Hepatoma Res 4:|
|Yang, Li; Palliyaguru, Dushani L; Kensler, Thomas W (2016) Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane. Semin Oncol 43:146-153|
|Watson, Sinead; Chen, Gaoyun; Sylla, Abdoulaye et al. (2016) Dietary exposure to aflatoxin and micronutrient status among young children from Guinea. Mol Nutr Food Res 60:511-8|
|Ravindra, Kodihalli C; Trudel, Laura J; Wishnok, John S et al. (2016) Hydroxyphenylation of Histone Lysines: Post-translational Modification by Quinone Imines. ACS Chem Biol 11:1230-7|
|Chao, Ming-Wei; Erkekoglu, P?nar; Tseng, Chia-Yi et al. (2015) Protective effects of ascorbic acid against the genetic and epigenetic alterations induced by 3,5-dimethylaminophenol in AA8 cells. J Appl Toxicol 35:466-77|
|Techapiesancharoenkij, Nirachara; Fiala, Jeannette L A; Navasumrit, Panida et al. (2015) Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B1. Toxicol Appl Pharmacol 282:52-60|
|Shirima, Candida P; Kimanya, Martin E; Routledge, Michael N et al. (2015) A prospective study of growth and biomarkers of exposure to aflatoxin and fumonisin during early childhood in Tanzania. Environ Health Perspect 123:173-8|
|Hernandez-Vargas, Hector; Castelino, Jovita; Silver, Matt J et al. (2015) Exposure to aflatoxin B1 in utero is associated with DNA methylation in white blood cells of infants in The Gambia. Int J Epidemiol 44:1238-48|
|Chawanthayatham, Supawadee; Thiantanawat, Apinya; Egner, Patricia A et al. (2015) Prenatal exposure of mice to the human liver carcinogen aflatoxin B1 reveals a critical window of susceptibility to genetic change. Int J Cancer 136:1254-62|
|Castelino, Jovita M; Routledge, Michael N; Wilson, Shona et al. (2015) Aflatoxin exposure is inversely associated with IGF1 and IGFBP3 levels in vitro and in Kenyan schoolchildren. Mol Nutr Food Res 59:574-81|
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