Open AccessJournal Article
Aflatoxins as a cause of hepatocellular carcinoma.
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TLDR
Much remains to be learnt about the precise pathogenetic mechanisms responsible for aflatoxin B1-induced hepatocellular carcinoma as well as the interaction between the toxin and hepatitis B virus in causing the tumor.Abstract:
Aflatoxins, metabolites of the fungi Aspergillus flavus and Aspergillus parasiticus, are frequent contaminants of a number of staple foods, particularly maize and ground nuts, in subsistence farming communities in tropical and sub-tropical climates in sub-Saharan Africa, Eastern Asia and parts of South America. Contamination of foods occurs during growth and as a result of storage in deficient or inappropriate facilities. These toxins pose serious public health hazards, including the causation of hepatocellular carcinoma by aflatoxin B1. Exposure begins in utero and is life-long. The innocuous parent molecule of the fungus is converted by members of the cytochrome p450 family into mutagenic and carcinogenic intermediates. Aflatoxin-B1 is converted into aflatoxin B1-8,9 exo-epoxide, which is in turn converted into 8,9-dihydroxy-8-(N7) guanyl-9-hydroxy aflatoxin B1 adduct. This adduct is metabolized into aflatoxin B1 formaminopyrimidine adduct. These adducts are mutagenic and carcinogenic. In addition, an arginine to serine mutation at codon 249 of the p53 tumor suppressor gene is produced, abrogating the function of the tumor suppressor gene, and contributing to hepatocarcinogenesis. Aflatoxin B1 acts synergistically with hepatitis B virus in causing hepatocellular carcinoma. A number of interactions between the two carcinogens may be responsible for this action, including integration of hepatitis B virus x gene and its consequences, as well as interference with nucleotide excision repair, activation of p21waf1/cip1, generation of DNA mutations, and altered methylation of genes. But much remains to be learnt about the precise pathogenetic mechanisms responsible for aflatoxin B1-induced hepatocellular carcinoma as well as the interaction between the toxin and hepatitis B virus in causing the tumor.read more
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References
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Journal Article
Oxy-radical induced mutagenesis of hotspot codons 248 and 249 of the human p53 gene.
TL;DR: It is evident that H2O2/FeCl3 possesses essentially the same mutagenic specificity for codons 249 and 250 of p53 as bulky carcinogens such as aflatoxin B1, benzo(a)pyrene or heterocyclic amines.
Journal ArticleDOI
High frequency of promoter hypermethylation of RASSF1A and p16 and its relationship to aflatoxin B1-DNA adduct levels in human hepatocellular carcinoma
Yu Jing Zhang,Habibul Ahsan,Yu Chen,Ruth M. Lunn,Li Yu Wang,Shu Yuan Chen,Po-Huang Lee,Chien-Jen Chen,Regina M. Santella +8 more
TL;DR: The hypothesis that exposure to environmental carcinogens may be involved in altered methylation of genes involved in cancer development is suggested by investigating promoter hypermethylation of RASSF1A and p16 in hepatocarcinogenesis.
Journal ArticleDOI
Molecular epidemiology of human liver cancer: insights into etiology, pathogenesis and prevention from The Gambia, West Africa.
TL;DR: In this paper, a review of decades of collaborative research centered in The Gambia, West Africa, explores the independent and combined effects of hepatitis B virus (HBV), hepatitis C virus (HCV) and dietary aflatoxin exposure in the etiology of hepatocellular carcinoma (HCC).
Journal ArticleDOI
Dominant contribution of P450 3A4 to the hepatic carcinogenic activation of aflatoxin B1.
TL;DR: The variable expression of P450s has a major effect on the carcinogenic activation of AFB1, which may affect the individual predisposition to HCC.
Journal ArticleDOI
Hepatitis B infection and aflatoxin biomarker levels in Gambian children
TL;DR: To examine the relationship between hepatitis B virus (HBV) infection and biomarkers of aflatoxin exposure in West African children, a large number of children diagnosed with HBV in the region have had prior exposure toflatoxin.
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