Kensler T W, Gange S J, Egner P A, Dolan P M, Muñoz A, Groopman J D, Rogers A E, Roebuck B D
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
Cancer Epidemiol Biomarkers Prev. 1997 Aug;6(8):603-10.
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.
针对动物和人类的研究已将血清黄曲霉毒素 - 白蛋白加合物确立为接触黄曲霉毒素B1（AFB1，一种食源性肝癌致癌物）的生物标志物。为评估黄曲霉毒素 - 白蛋白加合物测量值预测肝细胞癌（HCC）风险的效用，123只雄性F344大鼠在随机分为三组后，每天给予20微克AFB1，持续5周：无干预；延迟 - 短暂性干预（相对于AFB1给药的第2周和第3周给予500 ppm的奥替普拉）；或持续性干预（从第 - 1周至第5周给予500 ppm奥替普拉）。在整个黄曲霉毒素B1暴露期间，每周从每只动物采集系列血样，并通过放射免疫测定法检测黄曲霉毒素 - 白蛋白水平。与无干预组相比，延迟 - 短暂性和持续性奥替普拉干预组中黄曲霉毒素 - 白蛋白加合物的曲线下面积（AUC）值分别降低了20%和39%。同样，这些组中HCC的总发病率从83%降至60%（P = 0.03）和48%（P < 0.01）。两个奥替普拉干预组的肿瘤多发性也降低，而发生HCC的时间增加。单核细胞白血病是F344大鼠中的常见肿瘤，在39% 的对照动物中出现，而两个奥替普拉干预组将发病率分别降至18%（P = 0.05）和13%（P = 0.01）。总体而言，生物标志物AUC与HCC风险之间存在显著关联（P = 0.01）。然而，当在治疗组内评估黄曲霉毒素 - 白蛋白加合物的预测价值时，AUC与HCC风险之间无关联（P = 0.56）。因此，黄曲霉毒素 - 白蛋白加合物可用于监测干预措施（如化学预防试验）引起的基于人群的变化，但在识别注定会发生HCC的个体方面效用有限。因此，在定量风险评估中应谨慎使用这种生物标志物。
