TY - JOUR
T1 - Predictive value of molecular dosimetry
T2 - Individual versus group effects of oltipraz on aflatoxin-albumin adducts and risk of liver cancer
AU - Kensler, Thomas W.
AU - Gange, Stephen J.
AU - Egner, Patricia A.
AU - Dolan, Patrick M.
AU - Muñoz, Alvaro
AU - Groopman, John D.
AU - Rogers, Adrianne E.
AU - Roebuck, Bill D.
PY - 1997
Y1 - 1997
N2 - 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 μg 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 AUZ 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.
AB - 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 μg 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 AUZ 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.
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M3 - Article
C2 - 9264273
AN - SCOPUS:0030814179
SN - 1055-9965
VL - 6
SP - 603
EP - 610
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 8
ER -