Monitoring of aflatoxin exposure by biomarkers

Abstract

Epidemiological studies have demonstrated a strong association between exposure to AFB1 and an increased incidence of human hepatocellular carcinoma (HCC). This association has led to a need for accurate techniques relating AF exposure to an individual's risk of developing disease. With the understanding of the progressive processes of carcinogenesis, opportunities for the identification of molecular biomarkers reflecting events from exposure through clinical disease are provided. However, the development of biomarker methods to monitor human exposure to AFs requires techniques which are sensitive, specific, and amenable to large numbers of samples. To better understand the role of AF exposure with respect to HCC incidence, immunoassays for the biological quantitation of free AFB1, its metabolites, and its adduct macromolecules have been developed. ELISA appears to offer a suitable method for use in epidemiological studies for monitoring short-term exposure to AFs, as it has the appropriate sensitivity and specificity. However, the presence of substances that are presumably not AFs and which are inhibitory in the ELISA system has necessitated the development of purification techniques, usually based on adsorption onto Sep-Pak C18 cartridges and immunoaffinity chromatography. Many protocols have been developed for the assay of soluble AF metabolites in urine, milk and blood. However, these assays only indicate recent exposure, whereas the presence of albumin-AFB1 adducts in peripheral blood could present a useful material for assessing longer-term exposure. Among the various possible biomarkers of AF exposure, the measurements of AF-DNA and -protein adducts are of major interest because they are direct products of damage to a critical cellular macromolecular target. In Thailand, AF contamination of foods was reported to be high. More recent data using biomarkers as measures of AF exposure will be discussed. The data from epidemiological studies, AF exposure assessment using AF-albumin adduct and urinary AF level as exposure markers as well as the prevalence of p53 mutation at codon 249 are all suggestive of a limited importance of AF in the etiology of HCC in this country compared to other areas, including parts of Africa and China. These results also indicate that research on other potential hepatocarcinogens should not be neglected.