AFLATOXIN B-1 AND POLYCYCLIC AROMATIC HYDROCARBON ADDUCTS, P53 MUTATIONS AND P16 METHYLATION IN LIVER TISSUE AND PLASMA OF HEPATOCELLULAR CARCINOMA PATIENTS

Elevated aflatoxin B-1-albumin adducts (AFB(1)-Alb) have been associated with an increased risk for HCC development. However, there are no studies in humans, correlating albumin adducts in blood with liver DNA adducts. Forty frozen tumor tissues and 39 paired plasma samples from HCC patients were collected in Taiwan, to determine the relationship between albumin adducts in blood and DNA adducts in liver tissue as well as mutations in p53 and methylation of p16. AFB(1)- and polycyclic aromatic hydrocarbon (PAH)-DNA adducts in tissue and albumin adducts in plasma were determined by immunohistochemistry and competitive ELISA, respectively. Plasma AFB(1)-Alb adducts in subjects with low, medium and high levels of AFBI-DNA adducts in tumor tissues were 51.0 + /- 36.5, 70.5 +/- 48.1 and 84.9 +/- 48.2 fmol/mg, respectively (P-trend = 0.05). No significant correlation was found for PAH. Fourteen of 40 (36%) tissues were positive for mutant p53 protein by immunohistochemistry; 11 of 40 tissue DNA samples (28%) were positive for p53 mutations, but not their corresponding plasma DNAs. p16 was methylated in 24 of 40 (62%) tissues and 12 of 39 (32%) plasma DNAs. Significant correlations were observed between AFB(1)-Alb adducts and p53 mutations and p16 methylation. These data suggest that genetic, epigenetic and environmental exposure biomarkers in plasma may help in estimating the risk for the development of HCC. (c) 2006 Wiley-Liss, Inc.