Aflatoxins: a cause of hepatocellular carcinoma

Liver cancer is the 3rd leading cause of death by cancer worldwide and its incidence is rising at elevating rates and has become a public health concern globally. The most common cause of hepatocellular carcinoma are aflatoxins.

AflatoxinsAflatoxins are the byproducts of fungi that are found on agricultural crops like maize, peanut, cottonseed and tree nuts. Main fungi which produce aflatoxins are Aspergillus flavus and Aspergillus parasiticus which are abundant in warm and humid region of world. That fungi contaminate the crop in field, during harvesting and during storage.

There are more than 14 types of aflatoxins but AFB1, B2, G1, G2 are more common and carcinogenic to human and animals. AFB1 is most important hepatotoxic and hepatocarcinogenic which cause toxicity, teratogenicity, mutagenicity and carcinogenicity.

The international agency for research on cancer (IARC) calls AFB1 as well-known carcinogenic agent within goup-1 carcinogens for liver cancer. Its standard level is 10-20ng/g.

How human and animals exposed to aflatoxins:

Animals exposed to aflatoxins by eating crop products and by eating feed made b these contaminated crops. Human exposed to these toxins by eating these plant products and animal products that fed on contaminated feed, like egg, meat and milk and by inhaling the dust during processing and handling of crops.

Metabolism in the body:

When aflatoxins enter in the body they are metabolize in the liver by the cytochrome-P450 enzymes and produce reactive oxygen species Aflatoxin 8,9-epoxide(AFBO) detoxified by conjugation to glutathione by GST (Glutathione S transferase) in animals and hydrolysis to dehydration by microsomal epoxide hydrolase(mEH) in human.

When aflatoxin’s amount increases from bearable limit and when there is a continuous exposure to the aflatoxins will leads, AFBO will binds to the proteins and cause necrosis of the hepatocytes and that leads to hepatotoxicity that in chronic cases convert to cirrhosis.

Mechanism of carcinogenicity:

AFBO binds to DNA and forms the DNA adducts (N7 guanyl-9 and AFB-N7 Gua) which leads to genetic change in the target cell which cause DNA strand breakage, DNA base damage and oxidative damage which ultimately leads to cancer.

DNA adducts are formed due to the covalent bonding of AFBO to the N7 atom of guanine in the site-specific sequence leading to the mutation in the 249 codons of P53 tumor suppressing gene.

Mutated R249Sp53 cause stimulation of liver cell growth and produce hepatocarcinogenicity if it’s not repair before replication. AFB1 also cause immunosuppression that predispose the infection mostly hepatitis B and C virus which further damage the liver and add its part in causing liver cancer.

Preventive measures:

Exposure of aflatoxins can be prevented by avoid contamination at 2 levels. 1st is at preharvest level by increasing the resistance of plants against that fungi and prevent production of aflatoxins by invading fungi which is possible through plant breeding or genetic engineering of crop of interest so it’s a long-term process.

Can prevent its contamination through the biological control method by using the non-toxigenic A. flavus isolates. That strains have capability to compete and displace the toxigenic strains.2nd is at post-harvest level by providing adequate conditions (moisture, temperature, chemical or insect damage and aeration) which influence contamination and toxin production by fungi.

Other measures like chemical decontamination or use of enterosorbants, can be used to remove the toxins from already contaminated feedstuff.

Authors: Farwa Rabab *1, M. Tariq Javed1, Aisha Khatoon 1, Ashiq Ali1, Ifra Siraj1, Shunazia Saquib 1, Sania Saeed1.

1 Department of Pathology, Faculty of Veterinary Science, University of Agriculture Faisalabad, Pakistan.

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