Determinants of formation of aflatoxin-albumin adducts: a seven-township study in Taiwan

Abstract

Dietary exposure to aflatoxins is one of the major risk factors for hepatocellular carcinoma. Individual susceptibility to aflatoxin-induced hepatocarcinogenesis may be modulated by both genetic and environmental factors affecting metabolism. A cross-sectional study was performed to evaluate determinants of the formation of aflatoxin covalently bound to albumin (AFB 1 -albumin adducts). A total of 474 subjects who were free of liver cancer and cirrhosis and were initially selected as controls for previous case -control studies of aflatoxin-induced hepatocarcinogenesis in Taiwan, were employed in this study. Aflatoxin-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen and antibodies to hepatitis C virus by enzyme immunoassay, as well as genotypes of glutathione S-transferase M1-1 and T1-1 by polymerase chain reaction. The detection rate of AFB 1 -albumin adducts was significantly higher in males (42.5%) than in females (21.6%) (multivariate-adjusted odds ratio=2.6, 95% confidence interval=1.4 -5.0). The formation of detectable albumin adducts was moderately higher in hepatitis B surface antigen carriers (42.8%) than in non-carriers (36.6%) (multivariate-adjusted odds ratio=1.4, 95% confidence interval=1.0 -2.1). In addition, the detection rate of AFB 1 -albumin adducts tended to increase with the increasing number of null genotypes of glutathione S-transferase M1-1 and glutathione Stransferase T1-1. In conclusion, this cross-sectional study has assessed the relative contributions of environmental exposure and host susceptibility factors in the formation of AFB 1 -albumin adducts in a well characterised Chinese adult population. This study further emphasises the necessity to reduce aflatoxin exposure in people living in an area endemic for chronic hepatitis B virus infection.

Associated Factors in Modulating Aflatoxin B1?Albumin Adduct Level in Three Chinese Populations

“…This is consistent with an earlier observation in Taiwanese (26), in which the detection rate of AAA of males (42.5%) was significantly higher than that of females (21.6%) (OR = 2.6, 95% CI = 1.4-5.0). Nevertheless Chen et al (9) found a significantly higher level of AAA among female Taiwanese adolescents (age 13-15 years) compared with males.…”

Relevance of the Deletion Polymorphisms of the Glutathione S-Transferases GSTT1 and GSTM1 in Pharmacology and Toxicology

“…Notably, when the interaction between aflatoxin exposure and GSTT1 genotype was considered, aflatoxin exposure by itself was not a significant determinant of HCC risk among chronic HBsAg carriers. These results pointed to the importance of gene-environment interactions in HCC development [122,123].…”

“…This type of tumour is seen at high frequencies in Southeast Asia and in Subsaharan Africa. In Taiwan, it is the leading cancer in males, and the fifth in females [122,123]. Aetiologically, it has been linked with both viral (hepatitis B/C) and chemical (aflatoxin B 1 ) factors.…”

Synthesis of 5,5,6,6‐D4‐L‐lysine‐aflatoxin Bl for use as a mass spectrometric internal standard

“…5,6 Because the t l/2 of AFB l -albumin adducts in blood is $20-fold longer than that of urinary metabolites ($24 h) such as the AFB l -N 7 -guanine adduct or AFB l -mercapturic acid, albumin adducts have been more often used as a biomarker of AFB l exposure and disease risk. [7][8][9][10][11][12][13] The structure of an aflatoxin adduct formed with lysine in albumin was first elucidated via a proof by synthesis using AFB l dibromide as the starting material. [14][15][16] Condensation of the dialdehyde tautomer of 8,9-dihydro-8,9-dihydroxy-AFB l with the e-amino group of N a -acetyl-lysine to form a Schiff base, followed by an Amadori rearrangement to an a-amino ketone was proposed to lead to the formation of the N a -acetyl-lysine-AFB l adduct over a 24 h period.…”