MOLECULAR BIOMARKERS FOR AFLATOXINS - FROM ADDUCTS TO GENE-MUTATIONS TO HUMAN LIVER-CANCER

Over the past 30 years there have been extensive efforts to investigat e the association between aflatoxin exposure and human liver cancer. T hese studies have been hindered by the lack of adequate dosimetry data on aflatoxin intake, excretion, and metabolism in people, as well as by the general poor quality of worldwide cancer morbidity and mortalit y statistics. These realities have spurred the efforts to develop new technologies to assess exposure status and risk for aflatoxins, and th ese agents are among the few environmental carcinogens for which quant itative risk assessments have been attempted. One of the goals of thes e risk assessments has been the development of primary acid secondary preventive intervention methods to lower the human health impact from aflatoxin exposures. The long-term goal of the research described here in is the application of biomarkers to the development of preventive i nterventions for use in human populations at high risk for cancer. Sev eral of the aflatoxin-specific biomarkers have been validated in epide miologic studies and are now available for use as intermediate biomark ers in prevention trials. The development of these aflatoxin biomarker s has been based upon the knowledge of the biochemistry and toxicology of aflatoxins gleaned from both experimental and human studies. These biomarkers have been utilized subsequently in experimental models to provide data on the modulation of the markers under different situatio ns of disease risk. This systematic approach provides encouragement fo r preventive interventions and should serve as a template for the deve lopment and validation of other chemical-specific biomarkers and their application to cancer or other chronic diseases.