Matt Baumann, Elizabeth Hervey, Corey LoveUniversity of New Mexico

Biology of Toxins 44529 April 2009

Aflatoxins are naturally occuring mycotoxins

Produced by two species of Aspergillus fungus:• A. flavus• A. parasiticus

18 different types of aflatoxins

Aspergillus is an opportunistic pathogen of stored food products

Aflatoxin B1 (AFB1) most common in cultures and in food products

History Affects a wide variety of animals, namely livestock and

humans

Originally described as “Turkey X Disease” in England in 1960 until it proliferated in other animals

FDA has established action levels regarding allowable content

The Food Additives Amendment of 1958 raised the question as to whether mycotoxins would fall under control of the FDA

Relevance of aflatoxins No animals have known immunity but humans have elevated

tolerance levels.

There is a separation of genetic and nongenetic damage caused by aflatoxins which are species specific.

Mice have relatively high tolerance level but adverse effects are seen in chicken, ducks, trout, dogs, guinea pigs, and monkeys.

Necrosis is most common. • More often seen in ducklings and turkeys exposed to aflatoxins.

Concern for Humans

Aflatoxins cause mutation of p53 gene

Mutated p53 gene can cause cell division to continue regardless of the mistakes in the DNA sequences

This can lead to CANCER!!!

Aflatoxins spread via colonization and contamination of crops such as maize, wheat, rice and cotton.

May contaminate vertebrate milk

Foods found in:• Peanuts and various other nuts• Corn• Cottonseed• Stored Food Products

Absorption Ingestion is the main route into the body

Gastrointestinal system will the be the first site of absorption

The toxin is found in three types of substrate:• Living plants• Non-living plant parts• Harvested seeds

All of which play important roles in agriculture, human resources and the existence of livestock

Distribution After ingestion, Aflatoxins are absorbed by the blood stream

Moved through the fluid compartments

Enters Intracellular Fluid Compartment to disrupt DNA and Protein Synthesis

Action

Aflatoxin→→→Epoxide ↑ P450

P53 gene can go through a mutation:

•Mutation from GC to TA•Occurs on third position of codon 249

•Mutated p53 allows cells to go through division despite transcription errors

Action Once converted, aflatoxins react with nucleic

acids

They react with guanine in DNA and RNA leading to depurination

Aflatoxins can inhibit protein and DNA synthesis

DNA damage can also be mutagenic

Metabolism

Biotransformation of Aflatoxin• Multi-pathway• Determines the toxicity of the aflatoxin• Dose that binds to DNA is determined by

how much of the aflatoxin is converted to the epoxide

Metabolism

Our bodily responses to aflatoxin:

Hepatic necrosis Tremorgenic Nephrotoxicity Ascites- peritoneal cavity fluid Hemorrhages of Lungs and Brain (Cerebral Edema and

Death) Carcinogenic

Excretion Urine - The main pathway for excretion

Milk

Feces

Everyone is affected

Livestock more so than humans

Irreversible; there is no cure or known immunities

Progress has been made in refining samples to be used for food• This process involves alkali refining, washing and

bleaching of vegetable oils

Relevance- Immediate, US and Worldwide

New Mexico• Importance of agricultural lifestyles involving livestock and crops

Crops and livestock losses• Financial impact on farming communities

US and Worldwide• Important for foreign trade purposes• Overall cost of regulatory and preventative programs

Relatively developed countries with food enforcement policies stand a significant chance of preventing aflatoxin ingestion

Implications for undeveloped countries

• Peoples in poor economic status have a slimmer reliance on caloric intake

• Food sources generally include more grain and products easier to come by

• Such products are main sources of Aflatoxins

• Lack of variety increases susceptibility

Broader Implications Limited food resources for humans- FAMINE?

Dairy industry would be hit hard as the toxin can be excreted through vertebrate milk

Conditions that favor fungal growth include extremely stressful environments

Humidity/Drought- ability to proliferate in a variety of conditions

Potential use for biological warfare- “Cancer Bombs”

Future Research: Effects of Global Warming on the ability of aflatoxins to

spread

Can aflatoxins be used as biomarkers? They are inactivated by a variety of reagents. Aflatoxins may therefore provide insight into the effects on health by environmental agents.

Preventing contamination? Can we control genetic resistance to adverse effects of aflatoxins?

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