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Molecular Biomarkers for Aflatoxins and Their Application to Human Cancer Prevention¹

The Johns Hopkins University, School of Hygiene and Public Health, Department of Environmental Health Sciences, Baltimore, Maryland 21205 [J. D. G., T. W. K.]; Massachusetts Institute of Technology, Division of Toxicology, Department of Chemistry, Cambridge, Massachusetts 02139 [G. N. W.]; and Dartmouth Medical School, Department of Pharmacology and Toxicology, Hanover, New Hampshire 03755 [B. D. R.]

The rapidly expanding understanding of the progressive processes of carcinogenesis provides opportunities for the identification of molecular biological markers reflecting events from exposure through clinical disease. These molecular biological markers can be classified into categories of markers of exposure reflecting the dose of toxic agents, markers of effect indicating a biological response to exposure, and markers of susceptibility providing information about the inherent sensitivity of individuals to the toxic agents. By definition some of these markers are chemical agent specific, such as a carcinogen-DNA or -protein adduct, while others are biological process specific, such as the altered expression of a gene. This article reviews the development and validation of molecular biomarkers of aflatoxins using experimental and human population studies. The development of molecular biomarkers for aflatoxins is based upon the extensive research database available about their metabolism, macromolecular adduct formation, and general mechanisms of action. The long-term goal of the research described in this paper is the application of aflatoxin biomarkers to the development of preventive interventions in human populations at high risk for liver cancer.