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Disclose Carcinogen Aflatoxin B1 Scientifically and technically.

Posted on July 29, 2019 by Josephine

Aflatoxin B1 (AFB1) is a derivative of dihydrofuran containing a difuran ring and a coumarin. Aflatoxin B1 is one of the most carcinogenic fungi among the chemicals known by people. It has strong carcinogenicity and mainly induces liver cancer.

Chemical properties in Aflatoxin B1

Aflatoxin is insoluble in water, hexane, ether and petroleum ether and is easily soluble in organic solvents such as methanol, ethanol, chloroform, acetonitrile, and dimethylformamide. The maximum solubility in water is less than 10 mg/kg. It is generally stable in a neutral solution, but it is slightly decomposed in a solution of strong acidic. If it is decomposed in a strong base aflatoxin B1 solution of pH 9-10 quickly, it will decompose into almost non-toxic salt, destroyed by alkali or strong oxidant easily. Its pure product is a colorless crystal, high-temperature resistance, decomposition temperature at 280°C. Ultraviolet light is destructive to low aflatoxin of concentration, but its internal structure cannot be changed. When the conditions of the external reaction are removed, it can be restored to its original state. Therefore, the effect of ultraviolet light on it is reversible. Under natural conditions, aflatoxin-contaminated food is very stable. Rice that is heavily contaminated with aflatoxin B1 can be stored in normal conditions for up to 20 years without decomposition at indoor temperature.

Absorption and metabolism in Aflatoxin B1

Aflatoxin B1 is the substance that mainly causes food contamination and can induce liver cancer in various animals such as humans, livestock, and fish. AFB1 is the main indirect carcinogen, which can exert carcinogenicity after metabolic transformation in vivo. The carcinogenicity of AFB1 in vivo is mainly divided into two major pathways, including direct carcinogenesis and indirect carcinogenesis by the transformation.

Direct carcinogenicity is mainly manifested in this process. After human or animal inadvertently ingests AFB1 food, AFB1 is directly absorbed by the intestinal system in the body and mainly absorbed by the duodenum. The unabsorbed part is excreted with the excretory system. The main organs contained AFB1 in the body are the liver, kidney, and intestinal system.

Indirect carcinogenesis is mainly manifested in this process. AFB1 absorbed by internal organs is metabolized by intracellular cytoplasmic microsomal oxidative enzymes in the body, and AFB1 appears oxidation reaction on demethylation, hydroxylation and ringing under the action of microsomal mixed functional and was converted to its various homologs such as AFM1, AFP1, AF1, and aflatoxin. In these substances, only AFB1 and AFM1 can bind to enzymes in the body, and all of the others are excreted in the form of urine. The remaining AFB1 and AFM1 can form AFB1-8 and 9-epoxide. These epoxides can undergo II phrase enzyme effect in the body and corresponding metabolic processes to form AFB1-thiol uric acid, and it finally can be excreted by urinary excretion smoothly in one part. And the other parts form proteins with AFB1 albumin conjugate, which remain in the blood or bind to DNA to form the corresponding AFB1 nucleic acid, stimulating human liver cancer factor and playing a carcinogenic property. If AFB1 is not regularly ingested, it accumulates slowly in the body. It is easily excreted to reduce the damage through breathing, urine, stool, etc., in the body.

The metabolism of AFB1 is more complex in the body and is generally metabolized in the liver and absorbed in the intestine. About 50% of AFB1 in food is absorbed in the duodenum. The unabsorbed AFB1 is excreted through the feces without particularly causing great damage to the body. The absorbed AFB1 is distributed in the liver mainly and in the kidney and a small amount of AFB1 is distributed in the mesenteric vein in the form of free AFB1 and it’s water-soluble metabolites. The metabolic process of AFB1 in vivo is shown in Figure 1. Figure 1 shows that the metabolism of AFB1 produced in the liver by I phrase drug-metabolizing enzymes in vivo (cytochrome P450 oxidase CYP450 superfamily members, such as CYP1A2, CYP3A4, CYP2A6, etc.), undergoes hydroxylation, demethylation and other metabolic reactions to produce metabolites, such as aflatoxin alcohol, AFP1, AFQ1 and AFM1, inactive in the latter of three.

They can be directly excreted in the urine or the form of glucuronic acid through the feces. Aflatoxin alcohol can be oxidized to AFB1 and AFM1. It can undergo epoxidation under the effect of cytochrome P450 oxidase to form the final carcinogen that can bind to cellular macromolecules (DNA or protein), namely AFB1-8,9-epoxide. The formation of AFB1-8, 9-epoxide, and its production binding to DNA, RNA or protein covalently plays a key role in acute and chronic poisoning. The highly carcinogenic epoxide can be metabolized by a body phase II enzyme, such as glutathione S-transferase (GST), uridine diphosphate-glucuronyltransferase or sulfotransferase. Glutathione S-transferase (GST) can bind AFB1-8,9-epoxide and glutathione, and it finally excreted in the urine. At the same time, AFB1-8,9-epoxide destroys the G:C base pair at the N7 guanine position on the DNA, forming an AFB1-N7-guanine adduct that causes cancer. AFB1-8,9-epoxy by interacts with albumin to form an AFB1-albumin adduct distributed in the blood.

Disclose Carcinogenic Aflatoxin B1 Scientifically and technically.

The toxic mechanism in Aflatoxin B1

The absorption and excretion of aflatoxin in the body are fast. If it is not a continuous intake in AFB1 along with food with a relatively low amount. About 10 days later, it will be excreted by various excretory systems. If the amount of intake is too large, it will cause  AFB1 acute poisoning and damage to the liver. AFB1 is currently known to have strong triad material in mutagenicity, carcinogenicity, and teratogenicity. AFB1 mainly harms the liver and kidney in humans and animals. Aflatoxin symptoms mainly reflect the various manifestation of hepatocyte lesions in liver necrosis and liver cancer.

AFB1 is absorbed and transformed into various gastrointestinal systems in the body and converted into various homologs of AFB1, such as AFM1, AFM2, AFP1, and AFQ under various reactions such as demethylation, epoxidation, and hydroxylation. These transformed substances can bind to various proteins or enzymes in the body, affect or change the nature of the egg, interfere with the normal protein mechanism to cause cancer of the cells. Besides, AFB1 and it’s transformed AFM1 also cause great harm to the nucleic acid substances in the body, which can affect and change the DNA and RNA synthesis in the body to achieve the normal activities of changing the normal inheritance in the body. When AFB1 enters the body, AFB1-N7-guanine conjugate is formed and the AFB1-lysine conjugate remained in the blood. These two substances are the main component of AFB1 in vivo to produce toxicity. The area with the high incidence in aflatoxin is coincidence with the area in high incidence in various liver cancers, which proves that AFB1 is of high carcinogenicity.

Carcinogenesis in Aflatoxin B1

AFB1 is one of the strongest carcinogenic chemicals at present, and the range of it’s carcinogenic is particularly wide, such as in poultry, livestock, and various primates. It can induce a variety of cancers such as cancer in the liver, kidney, lacrimal adenocarcinoma, rectal, small intestine and other parts and can also induce teratogenic. Its molecular mechanism of carcinogenesis mainly focuses on the activation of oncogenes and the inactivation of suppressing in tumor genes. AFB1 induces gene mutation of ras cancer in liver tissue. The gene mutation increases P21 to induce the incidence of liver cancer. Aflatoxins can also cause mutations in the P53 gene. The mutant P53 gene can lose its suppressor in tumor activity and acquire the properties of oncogenes and lead to the formation of tumors. According to research, P53 mutations are more common in some areas with high exposure of aflatoxin in China and southern Africa, while it is rarely found in North America, Europe, the Middle East, and Japan. It suggests that humans are a genetic susceptibility to carcinogenic aflatoxins in the environment.

Biosynthesis in Aflatoxin B1

The synthesis process of AFB1 is in this procedure. acetyl CoA (acetate CoA) → hexanoyl CoA ( hexanoyl CoA) → polyketide(PK) → norsolorinic acid (NOR) → averantin(AVN) →5-hydroxy-averantin(HAVN) →oxoaverantin(OAVN) →averufin(AVF) →versiconalhemiacetalacetate(VHA) →versiconal(VAL)→ versacolorinB (VERB)→ versicolorinA (VERA)→demethylsterigmatocystin (DMST)→Aspergillus variabilis (sterigmatocystin, ST) → O-Methylsterigmatocystin(OMST) → AFB1.

Effects on animal health

1. It can reduce growth and development in animals and will reduce and destroy nutrients in raw materials or feed. If the content of toxin is too large, the feed that intakes from animals will also decrease. Aflatoxins in the body can reduce the activity of certain pancreatic enzymes, affect the synthesis of enzymes and certain hormones and cause absorption, metabolism disorders, indigestion, loss of appetite, anemia, weight loss. Aflatoxins cause an increase in lipid levels in the liver and serum and cause a decrease in total protein, cholesterol and urea nitrogen in the blood.

2. It affects immune function. All animals use various conditions to protect themselves from various bacteria, viruses, fungi, parasites, and other external factors to ensure their health. This defensive ability requires the animal body having a complete and effective immune system to achieve. AFB1 affects humoral and cellular immunity, lowers serum protein and antibody levels, attenuates phagocytic cells, reduces body resistance to pathogenic microorganisms and reduces immunity.

3. It has an impact on reproduction ability in animals. The reproductive function of poultry is significantly affected by aflatoxin when the feed of poultry is contaminated by aflatoxin. The reproductive epithelium of male testis has obvious lesions, shrink in the testicles and become lighter and less to decreased rate of fertility and fertilization. When the content of AFB1 in the diet is 1 mg/kg, the weight of the egg is small and the rate of fertilization and hatching in the egg are affected. It will lead to the steatosis of the reproductive organs accompanied by inflammatory cell infiltration.

4. Carcinogenicity and teratogenicity of Aflatoxin B1 have classified as a grade-A carcinogen to humans by international authoritative organizations because of it’s great teratogenic and carcinogenic effects. The study found that AFB1 enters the body and mutates the P53 gene in cancer cells. It is scientifically proved that this gene can play a role in suppression of tumor and participate in cell regulation. The mutation of the P53 gene will change the spatial structure of its protein and lose the ability to repair auxiliary DNA fragments. It also promotes the canceration of cells.

5. Aflatoxin B1 directly affects the health of animals and people health. It will be transferred to livestock products (meat, milk, eggs) and threatens human health through the food chain. Acute poisoning of aflatoxin in humans often develops into acute hepatitis, bile duct hyperplasia, hepatocyte necrosis, and hepatic congestion, which is usually associated with eating food contaminated with aflatoxin. Typical changes may also occur toxic symptoms such as jaundice, fever, loss of appetite, anorexia, diarrhea, severe hepatosplenomegaly, liver pain, mucosal yellow staining, abnormal liver function, convulsions, and coma. If a small amount of aflatoxin is ingested, it will inhibit human growth, reduce food digestion, damage liver, induce liver failure, cause hepatitis B and cancer in cancer, stomach and intestinal in long-term formation of  In human body, AFB1 mainly undergoes metabolic processes such as demethylation and epoxidation, and metabolites are also toxic, carcinogenic and mutagenic. Aflatoxin is one of the causes of human primary liver cancer, stomach cancer, and lung cancer.

6. The impact of aflatoxin on the agricultural economy is a global problem facing all mankind. According to the Food and Agriculture Organization of the United Nations (FAO), 25% of the world's cereals are contaminated with mycotoxins every year, and aflatoxins are the most harmful ones. Many agricultural products and their products in our country are seriously polluted by aflatoxins, mainly including peanuts, corn, and feed produced by peanuts and corn. The World Health Organization (WHO) has set a corresponding standard for the content of AFT in foods, in which the total amount of aflatoxin B1, G1, B2, and G2 is not more than 15 μg/kg.

How to avoid aflatoxin and removal method in Aflatoxin B1

1. Physical and chemical methods can be this. The microwave-assisted alkali method can degrade aflatoxin to reach 98.5% in rice flour under certain conditions. AFB1 can be removed by ozone under certain conditions that when the content of moisture in peanut is 5%, the rate of detoxification is 65.88%.

2. The biodegradation method can be this. The biodegradation of Aflatoxin refers to the destruction in a group of toxins in AFB1 by certain substances produced by microorganisms during metabolism, so that AFB1 cannot be effectively synthesized in living organisms. Studies have shown that lactic acid bacteria, Bacillus, etc. can degrade AFB1. Lactic acid bacteria mainly reduce the content of AFB1 by adhesion, but this effect is reversible and is not suitable for practical production.

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