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The association between exposure to aflatoxin, mutation in TP53, infection with hepatitis B virus, and occurrence of liver disease in a selected population in Hyderabad, India.

Abstract
Aflatoxin B1 is a carcinogen produced by Aspergillus flavus and a few related fungi that are often present in many food substances. It interacts synergistically with Hepatitis B or C virus (HBV, HBC) infection, thereby increasing the risk of hepatocellular carcinoma (HCC). The G to T transversion at the third position of codon 249 (AGG) of the TP53 gene, substituting arginine to serine, is the most common aflatoxin-induced mutation linked to HCC. This study examined mutations in TP53 by PCR-RFLP analysis and by measurement of an aflatoxin-albumin adduct as a biomarker for human exposure of aflatoxin B1 by indirect-competitive ELISA, in samples collected from healthy controls as well as patients with hepatitis in Hyderabad, Andhra Pradesh, India. A total of 238 blood samples were analyzed the presence of the G to T mutation. Eighteen of these samples were from HBV-positive subjects, 112 of these were from subjects who had HBV-induced liver cirrhosis, and 108 samples were taken from subjects without HBV infection or liver cirrhosis (control group). The G to T mutation was detected in 10 samples, 8 of which were from subjects positive to both HBV and aflatoxin-albumin adduct in blood (p=0.07); whilst two were from individuals who were HBV-negative, but positive for the aflatoxin-albumin adduct (p=0.14). The aflatoxin-albumin adduct was detected in 37 of 238 samples, 29 samples were from HBV-positive subjects and eight were from individuals who were positive for both HBV and the TP53 mutation (p=0.07). The concentration of aflatoxin-albumin adduct ranged from 2.5 to 667pg/mg albumin. Despite low incidence of the G to T mutation, its detection in subjects positive to aflatoxin-adducts is indicative of a strong association between the mutation and aflatoxin exposure in India.
AuthorsS Anitha, D Raghunadharao, F Waliyar, H Sudini, M Parveen, Ratna Rao, P Lava Kumar
JournalMutation research. Genetic toxicology and environmental mutagenesis (Mutat Res Genet Toxicol Environ Mutagen) Vol. 766 Pg. 23-8 (May 15 2014) ISSN: 1879-3592 [Electronic] Netherlands
PMID24657665 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Aflatoxins
  • Carcinogens
  • Poisons
  • TP53 protein, human
  • Tumor Suppressor Protein p53
Topics
  • Aflatoxins (adverse effects)
  • Aspergillus flavus
  • Carcinogens (toxicity)
  • Female
  • Hepatitis B (chemically induced, epidemiology, genetics)
  • Hepatitis B virus
  • Humans
  • Incidence
  • India (epidemiology)
  • Male
  • Point Mutation
  • Poisons (adverse effects)
  • Polymorphism, Restriction Fragment Length
  • Tumor Suppressor Protein p53 (genetics)

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