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Metabolic activation of the hepatocarcinogenic mycotoxin aflatoxin B 1 (AFB 1 ) results in the covalent attachment of AFB 1 to serum albumin. Digestion of adducted albumin releases AFB 1 -lysine, a biomarker of exposure status. AFalbumin adducts have been most frequently measured in precipitated serum albumin using an immunoassay (ELISA); however, a sensitive and specific isotope dilution mass spectrometric (IDMS) assay for measurement of AFB 1 -lysine in serum has recently been developed. The ELISA and IDMS methods were compared using 20 human sera collected in Guinea, West Africa, where AF exposure is endemic. Measurement of AFB 1 -lysine adduct concentrations by IDMS in serum and albumin precipitated from the same sample revealed that precipitation has no effect on the measured adduct levels. The concentration of AF-albumin adducts measured by ELISA and AFB 1 -lysine measured by IDMS in 2 mg of albumin were well correlated (R = 0.88, P < 0.0001); however, AF-albumin adduct concentrations measured by ELISA were on average 2.6-fold greater than those of the AFB 1 -lysine adduct. Although these data suggest that the ELISA is measuring other AF adducts in addition to AFB 1 -lysine, these biomarkers are comparable in their ability to assess AF exposure at AF-albumin concentrations z3 pg AFB 1 -lysine equivalents/mg albumin. Identification of other adducts may clarify the mechanistic basis for using AFprotein biomarkers to assess exposure status in future epidemiologic studies of liver cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(4):823 -6)

Aflatoxins and hepatitis B virus (HBV) are major risk factors for hepatocellular carcinoma (HCC) in South-east Asia and Africa, parts of the world where this cancer is most prevalent. Exposure to both factors is endemic, occurring from early in life. There is evidence from both epidemiological studies and animal models that the two factors can act synergistically to increase the risk of HCC, but the underlying cellular and molecular mechanisms of interaction are as yet undefined. One possibility suggested by studies in HBV transgenic mice is that chronic liver injury alters the expression of carcinogen metabolizing enzymes, thus modulating the level of binding of aflatoxin to DNA. Primary prevention of HCC in high incidence areas of the world should primarily be focused on provision of the safe, effective vaccine against HBV. However, measures to reduce the high levels of aflatoxin exposure, where chronic HBV infection is currently epidemic, would also significantly contribute to reducing HCC incidence. In Guinea-Conakry, West Africa, surveys of HBV infection and aflatoxin exposure have established baseline data for the implementation of a community-based intervention study. This study will evaluate the effectiveness of improving the post-harvest processing and storage of the groundnut crop, a major source of aflatoxins, using aflatoxin-albumin adducts as the outcome measurement.

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