A PROPOSED METHODOLOGY OF CANCER RISK ASSESSMENT MODELING USING BIOMARKERS

Abstract

A methodology for cancer risk assessment modeling was developed using a biomarker of DNA adduct, exposure dose, and tumor response. DNA adducts in the blood and lung were measured after single or multiple administration of [3H]benzo[a]pyrene (1 2 BaP) in ICR mice. Making the assumption that DNA adducts are formed in a dose-dependent manner as observed in 1 2 BaP treatment, kinetics patterns of DNA adducts were predicted at two other hypothetical BaP doses (2 2 BaP, 1/2 2 BaP) for single and continuous BaP treatments because the difference between the simulated and the experimental kinetic responses only amounted to 5.49-5.86% in terms of the integrated area under the curve. Correlations between the formation of DNA adducts and exposure doses or between blood DNA and lung DNA adducts were determined to be linear. The doseresponse relationship between biomarker and exposure dose was further incorporated into a dose-tumor response equation, obtained from 2-yr bioassay, to predict cancer risk. The interrelationships between exposure dose, biomarker, and tumor response allowed the prediction of cancer risk in animals, once the information on biomarker levels was obtained. Moreover, this methodology could be further applied to human cancer risk assessment after appropriate safety factors were employed.