Exposure to aflatoxins

Both benign and malignant liver tumors may arise from exposure to hepatotoxins and can be derived from various cell types. Thus, adenomas have been associated with the use of contraceptive steroids and exposure to aflatoxin Bi, and dimethylnitrosamine can produce hepatocellular carcinomas, whereas vinyl chloride causes hemangiosarcomas derived from the vasculature (see chap. 7). 

Egal S, Hounsa A, Gong YY, Turner PC, Wild CP, Hall AJ, Hell K, Cardwell KF (2005) Dietary exposure to aflatoxin from maize and groundnut in young children from Benin and Togo, West Africa. Int J Food Microbiol, 104(2) 215-224. 

A connection has now been established between the occurrence of liver cancer and exposure to aflatoxin in the diet. Other factors are also known to be important (see box). High levels of exposure may also lead to acute hepatitis. 

The aflatoxins are a group of related mycotoxins produced by the mould Aspergillus flavus. There are four toxins, B, B2, G, and G2. The mould typically grows on crops such as grain and peanuts in hot, humid climates. There is evidence from epidemiology of an association between exposure to aflatoxin Bi in the diet and liver cancer in humans. Aflatoxin Bj is metabolized by the enzyme system cytochrome P450 in the liver to a chemically reactive metabolite (see pp. 19-23 and fig. 25), which reacts with molecules such as DNA and protein in liver cells. 

Olsen, J.H., Dragstedt, L., Antrnp, H. Cancer risk and occupational exposure to aflatoxins in Denmark. Brit. J. Cane. 1988 58 392— 396... 

The oral LD50 of Aflatoxin Bi is 9 mg kg in the mouse, 4.8 mg kg in the rat, and 10 mg kg in the hamster. Acute exposures to Aflatoxin Bi have been shown to cause liver damage in rodents. Dermal effects are apparent at 2-12 mg kg... 

Buss P, Caviezel M, Lutz WK. 1990. Linear dose-response relationship for DNA adducts in rat liver from chronic exposure to Aflatoxin Bi. Carcinogenesis 11 2133— 35... 

Garner RC, Dvorackova I. Tursi F. 1988. Immunoassay procedures to detect exposure to aflatoxin B-1 and benzo-a-pyrene in animals and man at the DNA level. Int Arch Occup Environ Health 60(3) 145-150. 

There is a direct association between the extent of exposure to aflatoxins in the diet and the prevalence of codon 249 Arg to Ser mutation. The most plausible interpretation of this association is that aflatoxins directly induce these mutations. This interpretation is supported by experimental studies showing that aflatoxin B1 binds at this codon and, preferentially induces this hotspot mutation in human cells in vitro. Moreover, the 249 Arg to Ser mutation is detected in the normal liver of aflatoxin-exposed individuals (Aguilar et al., 1993, 1994). 

Human exposure to aflatoxins occurs mainly through growth of the Aspergillus species A.flavus and A. parasiticus. Whether exposure is predominantly to aflatoxin Bl, or to mixtures of various aflatoxins, depends upon the geographical distribution of the strains. A.flavus, which produces aflatoxins Bl and B2, occurs worldwide, while A. parasiticus, which produces aflatoxins Bl, B2, G1 and G2, occurs principally in the Americas and in Africa. 

Unlike laboratory conditions where exposure of laboratory animals can be accurately defined, exposure of humans to aflatoxins cannot generally be estimated with any great certainty. Exposure to aflatoxin in tropical areas of Africa and parts of Asia and Latin... 

America can begin very early in life, and episodically thereafter, thus making accurate assessments of exposure extremely problematic. Furthermore, the number of episodes, and the degree of exposure to aflatoxin, varies greatly by country and region, by agricultural and crop storage practices, by season and by other factors difficult to control in any scientific study. 

Histories of probable poisoning with aflatoxins are described above in relation to the toxic episodes reported in Northwest India and Kenya. The case described below is of interest in that a full medical investigation and follow-up was performed which indicated that the patient remained well up to 14 years post-exposure. In addition, this case is extremely unusual in that a reasonably accurate estimate of exposure to aflatoxin can be made. 

The toxic effects from most alfatoxins are mostly on the liver including necrosis (cell death), cirrhosis and liver cancer. Most of these effects are chronic. Aflatoxin B1 is classified by lARC as a human carcinogen. A brief exposure to aflatoxins however, may produce a wide range of acute effects that may vary with the species, the subject s age, sex, nutritional condition, and the dose. 

Persistent viral infection by the hepatitis B or C virus (HBV or HBV) is probably the most important cause of HCC worldwide. Together with dietaiy exposure to aflatoxin Bl, they are responsible for about 80% of all HCCs in humans (Thorgeirsson and Grisham, 2002). In addition, males are afflicted at least twice as often as females, and its occurrence also increases progressively with age (Schafer and Sorrell, 1999 McGlynn et al., 2001). 

Immunoaffinify-Based Monitoring of Human Exposure to Aflatoxins in China and Gambia... 

Using epidemiological methods, the relationship between aflatoxln exposure and human liver cancer has been hindered by inadequate data on aflatoxln consumption, excretion, metabolism, and the general poor quality of world-wide cancer morbidity and mortality statistics. Molecular dosimetry methods are needed to help accurately assess an individual s exposure to aflatoxins. This is especially important because of the recent reclassification by the... 

Immunological Quantitation of Human Exposure to Aflatoxins and AT-Nitrosamines... 

Groopman, J. D. Kensler, T. W. The use of monoclonal antibody affinity columns for assessing DNA damage and repair following exposure to aflatoxin B i. Pharmac. Then, 34 321-34. 1987. 

Estimates of overall dietary exposure to aflatoxin—scenario with no MLs... 

A specific mutation in the p53 tumour suppressor gene has been detected in 10-70% of HCCs from areas of high AFBi exposure and is absent from HCCs from areas with negligible AFBi exposure [28-30]. Support for the implication that the mutation, a G- T transversion at the third base of codon 249, is caused by exposure to aflatoxin has come from in vitro studies. Aflatoxin exposure in bacteria almost exclusively causes G—transversions [31] and the aflatoxin-epoxide has been shown to bind to codon 249 of p53 in vitro [32]. Moreover, human... 

Viegas, S., Veiga, L., Malta-Vacas, J., Sabino, R., Figueredo, R, Almeida, A., et al. 2012. Occupational exposure to aflatoxin (AFBl) in poultry production. Journal of Toxicology and Environmental Health, Part A 15 1330-1340. 

In livestock, the consumption of aflatoxins in feed leads to a number of problems, which are then reflected in negative impacts on performance. Chronic exposure to aflatoxins leads to reduced growth and greater susceptibility to infections. This condition is often referred to as total failure to thrive. An extreme consequence of giving animals contaminated feed is lethal acute poisoning. 

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