How does aflatoxin cause cancer

Upon obtaining these numbers of all-cause liver cancer cases 1, and the total DALYs due to liver cancer 61, , the number of DALYs per capita case of 38 was calculated by dividing the latter by the former. The nationwide aflatoxin exposures ranged The highest median exposure was recorded for measures from Tabora median, Exposure ranges in Kilimanjaro were Table 3 shows the regional variation in patterns of exposures per quartiles of the exposure distributions.

The overall median nationwide population risk for aflatoxin-induced liver cancer was estimated to be 2. The median population risks cases per , persons varied from 1.

Based on these median population risks, the total number of aflatoxin-induced liver cancer cases per year as well as respective DALYs for Iringa, Kilimanjaro, Tabora and Tanzania, in general, were estimated and presented in Table 4. We estimated that in , the population risk cases per , people for aflatoxin-induced liver cancer in Tanzania was 2. We also estimated that the population risk in the studied regions varied from 1.

The risks estimated for Iringa, Kilimanjaro, Tabora and Tanzania are similar to risks recently reported for Borgou 7. All these countries have tropical climates which provide favorable conditions for mycotoxin contamination in foods maize and groundnuts, in particular.

The risk 6. We have previously reported that contamination of aflatoxins in maize flour consumed by the children from whom the biomarker data were generated was much more common in Tabora compared to Iringa or Kilimanjaro [ 14 ].

Such differences between regions reflect differences in climate and soil conditions. Tabora is one of the semi-arid regions of Tanzania. Drought is one of the factors predisposing crops to fungal infection and mycotoxin formation. Further, most people in Tabora consume groundnuts as staple food, and the crops is susceptible to aflatoxin contamination [ 29 ]. We estimated that in , Tanzania had 1, new cases of aflatoxin-induced liver cancer and that the total DALYs healthy life years lost due to these aflatoxin-induced liver cancer cases would be 56, These healthy life years could be saved if workable aflatoxin control measures are adopted in this country.

From risk management point of view, strict food regulations and effective enforcement are the best strategies, where possible. But, in subsistence farming communities such as those in Tanzania, amongst many other mitigation methods explored, to date the best option to minimize the risk of aflatoxins contamination and exposure is adoption of good agricultural practices including biocontrol technology during pre-harvest and post-harvest stages of food management including appropriate storage.

Bandyopadhyay et al. Also, it was demonstrated by Wu and Khlangwiset [ 16 ] for Nigeria that, at an upper estimate, if that technology is adopted up to , DALYs will be saved annually.

Wu and Khlangwiset [ 16 ] showed further that if the post-harvest intervention package tried by Turner at al. The post-harvest intervention package consisted of six components which are cheap and available to most Tanzanians. The components are education on hand-sorting of nuts, natural fibre mats for drying the nuts, education on proper sun-drying, natural-fibre bags for storage, wooden pallets on which to store bags, and insecticides applied on the floor of the storage facility under the wooden pallets [ 28 ].

These examples demonstrated the extent of healthy life years that can be saved in Nigeria and Guinea if those countries adopted these measures to prevent aflatoxin-induced liver cancer. Although the estimates for Nigeria and Guinea are not directly transferable to the Tanzania situation, they show that adoption of these cost-effective interventions requires fewer resources than can be served through minimized risks of aflatoxin exposure and liver cancer.

As for setting and enforcing appropriate maximum limits for aflatoxins in food, Abt Associates Inc. However, it should be noted that implementation of standards is a challenge because majority of the people in developing countries like Tanzania consume their own grown foods or locally unpackaged foods, which are not formally regulated. Other options for minimizing the risk of aflatoxin contamination and exposure include diversification of diet to reduce consumption of aflatoxin prone foods, removal of toxins through means like sorting and screening at household level and vaccination of the general population against Hepatitis B and C Viruses to minimize the risk of liver cancer development [ 8 ].

We estimated the annual aflatoxin-induced liver cancer cases in Tanzania using biomarker data. In Tanzania, the aflatoxin biomarker data was derived from children. The use of these dataset was with a strong assumption that they represent the aflatoxin exposure in the entire populations of Tanzania in Nonetheless, it is worth noting that although Shirima et al. The use of data from children to estimate the burden of aflatoxin-induced liver cancer is also warranted by the fact that a recent study by the Africa Liver Cancer Consortium shows that liver cancer tends to develop at a younger age in Africa than in other regions of the world [ 31 ].

It is not possible to know the actual exposure that contributed to liver cancer incidence in , but the biomarker data provides the best source of data for making an estimation.

These data measure exposure over a period including different seasons and in three geographical regions, so give an integrated estimate of exposure in Tanzania.

The total number of aflatoxin-induced liver cancer cases per year was estimated to be 1, The burden of aflatoxin-induced liver cancer is consistent with the high rates of HBV infection and aflatoxin exposure in this country.

The subjects from whom the biomarker data were obtained consumed a diet that was predominantly maize based [ 14 ]. We previously reported a significant correlation between the dietary intake of aflatoxins and the blood aflatoxin biomarker levels [ 34 ]. It may also be seen from Table 3 that aflatoxin exposure varies among individuals in the country. The reasons for the variation were discussed in detail by Shirima et al.

Exposure is likely to be higher in areas where drought, high temperature, low soil fertility, pest infestation and other stresses are common, as these factors affect plant growth and vigor, thus increasing the likelihood of fungal infection, as well as the levels of aflatoxins produced by the Aspergillus fungi [ 9 ].

In addition, households that cannot afford a diversified diet are at a higher risk of aflatoxin exposure because their per capita consumption of aflatoxin prone foods is higher [ 10 ]. In addition to liver cancer, aflatoxin exposure is associated with other health effects such immune suppression [ 35 ] and stunting [ 14 , 36 , 37 ]. We estimated aflatoxin-related health impacts for liver cancer only, because this is the only endpoint for which a clear etiology mechanism is established [ 5 , 6 ].

We also estimated DALYs related to aflatoxin-induced liver cancer as an attempt to present the aflatoxin problem in a language that can be appreciated by policy makers. Therefore, the results presented here may be an underestimate of the total impact of aflatoxin contamination in Tanzania. The overall intention is to trigger more policy actions for mitigation of the aflatoxin problem in the country as well as other countries of Africa where aflatoxin exposure is a problem.

This evidence is important because in the absence of aflatoxicosis outbreak it is very difficult for policy makers to understand the magnitude of the health impacts of chronic exposures to aflatoxins as the toxins are not visible and the impacts such as liver cancer manifest long after the exposure. We understand the importance of health-related economic impacts of aflatoxin exposure, but due to limited resources we could not include them in this assessment.

The economic impacts include raised demand for medical services, falling labor efficiency, the time sufferers spend seeking medical attention, and the time spent by family members attending to the sick. Liu and Wu estimated that up to The Global Disease Burden Project of reported the total number of all-causes liver cancer for Tanzania as 1, [ 26 ]. Generally aflatoxins have been reported to depress growth and alter many aspects of humoral and cellular immunity and thus affecting the hematological parameters [ , ].

Different parts of the nephrone are exposed to aflatoxins especially the AFB 1 and its metabolites leading to nephrotoxicity before it is excreted in the urine [ 24 , 58 ].

The aflatoxin induced reduction in protein content has been reported to be due to increased necrosis of the kidney [ 58 - 60 , 90 ]. There were also renal lesions with features of megalocytosis in the proximal renal tubules. In Africa, birds exposed to AFB 1 were reported to develop fatty and hemorrhagic kidney syndrome, thickening of the glomerular basement membrane, abnormal development of glomerular epithelial cells and degenerative changes in renal tubular cells, congestion and parenchyma hemorrhage [ 24 , 85 ].

In other animals, there was a reduction in the glomerular filtration rate, glucose reabsorption and tubular transport of electrolytes and organic anions, reduced activities of renal glutamate-oxaloacetate and pyruvate transaminases and alkaline phosphatase in rats attributed to by the aflatoxins and their metabolites as well as the generated ROS.

There was induced aggregation and loss of chromatin, mitochondrial degeneration and loss of microvilli induced by AFB1 in cultured kidney cell lines [ 24 , 85 ]. Aflatoxin especially AFB has been reported to interfere with the functioning of the various endocrine gland by disrupting the enzymes and their substrates that are responsible for the synthesis of the various hormones. Aflatoxins and their metabolites as well as the generated ROS have been reported to cause various cancers in different endocrine glands like pituitary gland, granulosa cell tumors of the ovary and adenomas and adenocarcinomas of the adrenal gland, kidneys, thyroid gland, ovaries, testes, thyroid gland, parathyroid glands and endocrine pancreas [ 4 , 90 , ].

The plasma testosterone and luteinizing hormone LH concentrations have been reported to reduce in aflatoxin-fed birds [ 90 ]. In laboratory animals, aflatoxin causes delayed maturation of both males and females [ 4 , 22 , 90 , ].

Aflatoxicosis in white leghorn males chicken decreased feed consumption, body weight, testes weight and semen volume Sharlin et al. In humans exposed to chronic aflatoxin-contaminated foods, it has been reported that higher concentrations of aflatoxins occur in the semen of infertile men [ 3 ]. It is also associated with low birth weight, a risk factor for jaundice in infants as well as presence of AFM in maternal breast milk where it can cause deleterious effect in the newborns [ ].

Aflatoxins have been reported to disrupt the reproductive system in both male and female animals after ingestion of aflatoxin-contaminated foods. Aflatoxins also cause pathological alterations in the form of coagulative necrosis especially in the growing and mature follicles and decrease in number and size of graffian and growing follicles with increased number of atretic follicles and small areas of degenerative changes in experimental animals [ ].

AFB 1 has been reported to have a deleterious effect on the reproductive capacity of laboratory and domestic female animals where they cause reductions in ovarian and uterine sizes, increases fetal resorption, implantation loss and intra-uterine death in the aflatoxin exposed female rats [ ].

They also cause a reduction in the primary spermatocytes and spermatids [ ] and affect the morphology of the sperm cells produced [ ]. Stillbirths were reported in the 15th to the 18th days of pregnancy in rats [ ]. The levels of plasma testosterone, plasma 5a-DHT and absolute and relative testes weights were reported in experimental animals of aflatoxin-treated males remained low in all age groups and a delay in the onset of sexual maturation during aflatoxicosis [ ].

In cows, aflatoxins affected the reproductive system by causing abortion, the birth of weak, deformed calves, reduced fertility due to reduced vitamin A levels [ ]. The teratogenic effects of AFB 1 were described as enlarged eye sockets and enlarged liver of embryos [ 60 ]. In poultry, AFB1 cause a reduction in semen volume, testes weight, spermatocrit and plasma testosterone as well as a reduction in egg output [ 24 ].

Chronic consumption of aflatoxin-contaminated foods has been reported to cause immunosuppression in both humans and animals worldwide [ 7 , 89 ].

In human, aflatoxins affect both the cellular and humoral immune responses where they alter immunological parameters in participants with high AFB 1 levels resulting in impairments in cellular immunity hence decreasing the host resistance to infections [ - ]. Aflatoxin exposure has been shown to cause immune suppression, particularly in cell-mediated responses [ - ]. Chronic exposures of the individual to aflatoxins depress the phagocytic efficiency of the phagocytes and the delayed hypersensitivity reactions in birds [ 24 ].

Aflatoxins also deplete the cell populations of the thymus; reduce the bone marrow and the red and white blood cells count, macrophage numbers and the phagocytic activity of the cells [ 24 ]. It also depresses the T-cell-dependent functions of splenic lymphocytes in mice. The natural killer cell function of the peripheral blood lymphocytes are also affected by aflatoxins especially AFB1 [ 24 ].

Children in developing countries appear to be naturally exposed to aflatoxin through their diet at levels that compromise the immune system. In general, the proportion of childhood growth stunting is directly correlated with the proportion of the population living below the national poverty line and is inversely correlated with gross domestic product per capita [ 7 , 45 ].

As is the case with liver cancer, childhood stunting is prominent in regions such as Southeast Asia and Sub-Saharan Africa, where aflatoxin exposure through consuming contaminated food is common [ 7 , 45 ]. It has been reported that the immunosuppression and nutritional effects of chronic aflatoxin exposure may be linked to the high prevalence of HIV in Southern Africa [ 7 , 74 , , ]. The CD4 proteins that have been weakened by aflatoxin exposure have been reported to correlate positively with HIV infection [ ].

Also high aflatoxin levels have been reported to increase risk of developing tuberculosis in HIV positive individuals. Persons who are exposed to aflatoxin and are HIV positive have decreased plasma vitamin A and vitamin E in the blood, although there was no interaction detected between aflatoxin and HIV infection [ ]. HIV infection is likely to increase aflatoxin exposure by two possible routes: 1 HIV infection decreases the levels of antioxidant nutrients that promote the detoxification of aflatoxin, or 2 the high degree of co-infection of HIV-infected people with hepatitis B also increases the biological exposure to aflatoxin [ 7 , , ].

Aflatoxin induce immunosuppression and increases susceptibility of toxicated birds and animals to bacterial, viral and parasitic infections [ 58 ]. It also affects the lymphoid follicles of caecum thus depleting the lymphocytes that may contribute to the observed immunosuppression [ ].

Aflatoxin decreases the concentrations of immunoglobulins IgM, IgG and IgA in birds as well as decrease complement activity in chickens [ 22 , ].

Aflatoxin suppression of the immune system therefore subjects the individual to high risk of susceptible to infectious diseases like parasitic, bacterial and viral infections [ ].

Chronic consumption of aflatoxin-contaminated foods is a common problem in both humans and animals worldwide especially in poor developing nations of south East Asia and sub-Saharan Africa where there is poor food harvesting, processing and storage of food and food products thus allowing the growth of mold on them.

Aflatoxins, their metabolites, the aflatoxin-8,9-epoxide and the generated ROS causes deleterious effects on the various body organs and body systems including the development of cancers especially the liver cancer mainly due to AFB 1 exposure.

Aflatoxins are also responsible for the suppression of both the humoral and cell-mediated immunity and thus making individuals susceptible to infectious diseases. Aflatoxins also responsible for the malabsorption of various nutrients thus leading to nutritional deficiencies, impaired immune function, malnutrition and stunted growth and hence the development of kwashiorkor and marasmus in infants. Aflatoxins also can affect almost all the different body systems and hence the health of the affected individuals especially in poor developing nations of south East Asia and sub-saharan Africa where there is poor food harvesting, processing and storage thus allowing the growth of mold on them.

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Our readership spans scientists, professors, researchers, librarians, and students, as well as business professionals. Downloaded: Introduction Aflatoxins are a group of naturally occurring carcinogens that are known to contaminate different human and animal food stuffs. Table 1. Effect of aflatoxins on mitochondrial structure AFB causes ultrastuctural changes in mitochondria [ 46 - 49 ]and also induces mitochondrial directed apoptosis thus reducing their function [ 20 , 29 , 48 - 51 ].

Role of glutathione in detoxification of aflatoxins and their metabolites However like in hepatic detoxification of aflatoxins and other chemicals, GSH act as antioxidant and has many functions in membrane maintenance and stability as well as in reducing oxidative stress factors and the high reactive oxygen species ROS produced from the process of lipid peroxidation [ 38 - 41 , 46 , 52 - 56 ].

The role of cytoplasmic reductase in detoxification of AFB 1 Also in the hepatocytes, AFB 1 are converted to other different classes of metabolites by cytoplasmic reductase such as aflatoxicol and by microsomal mixed-function oxidase system to form AFM 1 , AGFQ 1 , AFP 1 and AFB 1 -epoxide the most toxic and carcinogenic derivative and these metabolites may be deposited in various body tissues as well as in edible animal products [ 38 - 41 , 46 , 52 - 55 ].

Effect of aflatoxins on protein synthesis The aflatoxin binds and interferes with enzymes and substrates that are needed in the initiation, transcription and translation processes involved in protein synthesis.

Role of aflatoxins in cancer Aflatoxins especially AFB 1 , AFG 1 and AFM 1 are the most toxic, naturally occurring carcinogens known with AFB 1 the most hepatocarcinogenic compound, causing various cancers of the liver and other body organs in humans and animals [ 4 , 14 , 45 , 61 ]. Role of aflatoxins in hepatic injury and other body organs and tissues Aflatoxins have been reported to cause liver cirrhosis as well as liver cancers [ 4 , 6 , 7 , 26 , 80 ].

Professor Kensler explains their clinical trials in which chlorophyllin was administered as a therapy and the resultant levels of aflatoxin DNA damage products present in urine samples. In this section learn about inexpensive and safe substances being investigated that may decrease the risk of liver cancer. Professor Kensler explains that there is a lot of interest in discovering new classes of chemopreventative agents and foods such as, fruits and vegetables appear to be a very rich source.

This section explains that lung cancer is the leading cause of cancer deaths in the United States and it is almost entirely preventable, since the vast majority of cases are due to cigarette smoking. In order to identify cancer causes and prevention strategies, researchers conduct a cohort of studies where they collect information from large groups of individuals over many years.

Causes, Mold: Aflatoxin action. Description Transcript Keywords Info Aflatoxin causes DNA damage and with prolonged exposure to aflatoxin, cells accumulate DNA mutations and thus are at increased risk of developing into cancer cells.

Related Content. Causes, mold Aflatoxin, a byproduct of molds, is a potent cancer-causing agent. ID: Source: IC. Frederick National Laboratory for Cancer Research. Bioinformatics, Big Data, and Cancer.

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