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Aflatoxin B1

Aflatoxin B1

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Aflatoxin B1

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  1. Aflatoxin B1

  2. Background

  3. Toxicity Parameters • Exposure to 2-6 mg of aflatoxin by consumption daily for one month is cited to have toxic effects (David et al. 1994) • Consumption of 55 µg/ kg of aflatoxin daily for an unknown period of time will be fatal (FDA 1992) • However, levels found to be toxic are inconsistent between various studies. Reasons for this include the fact that most studies were done in African countries where prevalence of Heptatitis B is very high. Active HepB virus is known to be synergistic with aflatoxin in causing toxicities and hepatocellular carcinoma. • As well, most studies were done on rats, which are much more susceptible to the toxin and its metabolites, and thus these studies cannot be extrapolated to humans.

  4. Mechanism of Action • AFB1 is oxidized by CYT P450 in the liver into AFB1-8,9-epoxide which is the major metabolite that exerts hepatotoxic effects

  5. AFB1-8,9-epoxide Is Cancer-causing!! • One of the most serious effects of the AFB1-8,9-epoxide metabolite is it reacts with amino acids in DNA and forms an adduct. This adduct is fairly resistant to DNA repair processes and thus this gene mutation may cause carcinoma of the liver. • CYP 3A4 is the major CYP 450 enzyme responsible for activation of AFB1 into the epoxide form. • - However, the liver can detoxify AFB1 by oxidizing it to other metabolites such as AFQ1 which has very little cancer-causing potential. These are usually excreted in urine with little effect on the body. (Novoa and Diaz 2006)

  6. What Exactly Does Aflatoxin Do? • Inactivation of p53 tumor suppressor gene enables mutation of Codon 249 (primary gene mutation caused specifically by AFB1). This shuts off the gene and potentially allows for uncontrolled cell proliferation. • But exposure to aflatoxin does not necessarily predispose you to liver cancer. The human body is capable of genetic repairs and there are differences in carcinogenic susceptibility among individuals in a population.

  7. In general, the incidence of toxicity and cancer is quite low after toxin exposure. The liver is very efficient in removing it from the body in most cases. Children are more susceptible to toxicity because their metabolic enzyme systems are not fully developed.

  8. Other Adverse Effects of AFB1-8,9-epoxide • Lipid accumulation in the liver due to decreased lipid transport and reduced oxidation which in turn reduces lipid synthesis (formation of membranes, etc.) • Jaundice, ascites (fluid build up), portal hypertension, and other symptoms of liver failure occur with acute aflatoxicosis

  9. Treatment • Inactivation of toxin before ingestion • Synergistic combination of gamma radiation and hydrogen peroxide degrades the toxin • Treatment of corn with ammonia • Dichlorvos inhibits aflatoxin B1 biosynthesis • NaHSO3 soak for corn also shows beneficial results • After ingestion • Treatment with antibiotics or other drugs has little effect • UV doses increased rate and extent of removal of aflatoxin B12 adducts from DNA • Chlorophyll intervention: supplement diets with foods rich in chlorophyll • Blocks carcinogen bioavailability • Certain types of flavanoids found in grapefruit stimulates the microsomal activation of aflatoxin B1 to the exo-8,9-epoxide which is not harmful • Administration of drugs that induce hepatic detoxification enzymes (ethoxyquin, butylated hydroxyanisol, butylated hydroxytuluene, phenobarbital) • Oltipraz inhibits aflatoxin B1 mediated hepatocarcinogens in rats • Induction of an antibody that would allow the body to identify and remove the toxin upon exposure (aflatoxin B1- lysine adduct monoclonal antibody)

  10. Literature Cited • Urrego Novoa JR and Diaz GJ. 2006. Aflatoxins and its mechanisms of toxicity in hepatic cancer. Rev.fac.med.unal. 54: 108-116. Available from World Wide Web: <http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0120-00112006000200006&lng=en&nrm=iso>. • Eaton DL and Gallagher EP. 1994. Mechanism of aflatoxin carcinogenesis. Annual review of pharmacology and toxicology 34: 135-172.