Studies in animals and humans have established serum
aflatoxin-
albumin adducts as
biomarkers of exposure to
aflatoxin B1 (AFB1), a food-borne hepatocarcinogen. To assess the utility of measurements of
aflatoxin-
albumin adducts to predict risk of
hepatocellular carcinoma (HCC), 123 male F344 rats were dosed with 20 microg of AFB1 daily for 5 weeks after randomization into three groups: no intervention; delayed-transient (500 ppm of
oltipraz, weeks 2 and 3 relative to AFB1); or persistent (500 ppm
oltipraz, weeks -1 to 5). Serial blood samples were collected from each animal at weekly intervals throughout
aflatoxin B1 exposure and assayed for levels of
aflatoxin-
albumin by radioimmune assay. Area under the curve (AUC) values for
aflatoxin-
albumin adducts decreased 20 and 39% in the delayed-transient and persistent
oltipraz intervention groups, respectively, as compared to no intervention. Similarly, the total incidence of HCC dropped from 83 to 60% (P = 0.03) and 48% (P < 0.01) in these groups.
Tumor multiplicity was also reduced in the two
oltipraz intervention groups, whereas time to HCC was increased. Mononuclear cell
leukemia, a common
neoplasm in F344 rats, was seen in 39% of the control animals, whereas the two
oltipraz interventions reduced incidence to 18% (P = 0.05) and 13% (P = 0.01), respectively. Overall, a significant association was seen between
biomarker AUC and risk of HCC (P = 0.01). However, when the predictive value of
aflatoxin-
albumin adducts was assessed within treatment groups, there was no association between AUC and risk of HCC (P = 0.56). Thus,
aflatoxin-
albumin adducts can be useful for monitoring population-based changes induced by interventions, such as in
chemoprevention trials, but have limited utility in identifying individuals destined to develop HCC. As a consequence, the use of this
biomarker in quantitative risk assessment should be pursued cautiously.