Molecular Mechanisms of Hepatocellular Carcinoma Related to Aflatoxins: An Update

Abstract

Hepatocellular carcinoma (hepatocarcinoma) is a major type of primary liver cancer and one of the most frequent human malignant neoplasms. Aflatoxins are I-type chemical carcinogen for hepatocarcinoma. Increasing evidence has shown that hepatocarcinoma induced by aflatoxins is the result of interaction between aflatoxins and hereditary factor. Aflatoxins can induce DNA damage including DNA strand break, adducts formation, oxidative DNA damage, and gene mutation and determine which susceptible individuals feature cancer. Inheritance such as alterations may result in the activation of protooncogenes and the inactivation of tumor suppressor genes and determine individual susceptibility to cancer. Interaction between aflatoxins and genetic susceptible factors commonly involve in almost all pathologic sequence of hepatocarcinoma: chronic liver injury, cirrhosis, atypical hyperplastic nodules, and hepatocarcinoma of early stages. In this review, we discuss the biogenesis, toxification, and epidemiology of aflatoxins and signal pathways of aflatoxin-induced hepatocarcinoma. We also discuss the roles of some important genes related to cell apoptosis, DNA repair, drug metabolism, and tumor metastasis in hepatocarcinogenesis related to aflatoxins.

X-Ray Repair Cross Complementing 4 (XRCC4) Genetic Single Nucleotide Polymorphisms and the Liver Toxicity of AFB1 in Hepatocellular Carcinoma

“…Our results exhibited HCC tumor samples from high AFB1 exposure areas have an average adduct amount of 2.27 AE 1.09 μmol/mol DNA. Supporting our findings, several studies from high AFB1 exposure areas Nanning and Tiandong, China, have also shown the similar level of DNA adducts [4,5,26,27,37,39,45]. Taken together, the amount of AFB1-DNA adducts should be able to reflect the hepatic toxic potential of AFB1.…”

“…Aflatoxin B1 (AFB1) is an important type I chemical toxicant mainly produced by the toxigenic strains of Aspergillus flavus (A. flavus) and Aspergillus parasiticus (A. parasiticus) [1,2]. This carcinogen is often taken into human body via contaminating human foods such as nuts and cereals and displays its toxic effects, especially hepatic toxicity [1][2][3][4][5][6][7][8]. AFB1-induced hepatic effects consist of acute toxic damages (such as severe DNA damage, severe liver degeneration and necrosis, and the failure of hepatic function) and chronic cumulative damages (such as a series of cumulative DNA damage, slight hepatocellular degeneration and necrosis, chronic inflammation, liver cirrhosis, and liver cancer) [3][4][5].…”

“…This carcinogen is often taken into human body via contaminating human foods such as nuts and cereals and displays its toxic effects, especially hepatic toxicity [1][2][3][4][5][6][7][8]. AFB1-induced hepatic effects consist of acute toxic damages (such as severe DNA damage, severe liver degeneration and necrosis, and the failure of hepatic function) and chronic cumulative damages (such as a series of cumulative DNA damage, slight hepatocellular degeneration and necrosis, chronic inflammation, liver cirrhosis, and liver cancer) [3][4][5]. Increasing evidence has shown that under the same exposure of AFB1, some individuals feature severe hepatic damage; others have no noticeable damage [9][10][11][12][13][14].…”

Single‐nucleotide polymorphisms in the coding region of a disintegrin and metalloproteinase with thrombospondin motifs 4 and hepatocellular carcinoma: A retrospective case‐control study

“…Given that aforementioned HBV infection and AFB1 exposure are two major causes for Guangxiese HCC, we questioned whether there were interactive effects between causes and ADAMTS4 SNPs and accomplished a series of joint analyses based on the combination of ADAMTS4 genotypes and causes (Table ). Results showed that these individuals with both positive status of causes and risk genotypes would face higher risk for HCC.…”

The Blood AFB1-DNA Adduct Acting as a Biomarker for Predicting the Risk and Prognosis of Primary Hepatocellular Carcinoma

“…Aflatoxin B1 (AFB1) is a knowledge I-type chemical carcinogen for primary hepatocellular carcinoma (PHCC) [1][2][3]. This carcinogen is mainly produced by Aspergillus parasiticus and Aspergillus flavus and often found in crops and food (including maize, nuts, and beans), which are raised in the areas with humid and hot environment [1,4,5].…”