matt baumann, elizabeth hervey, corey love university of new mexico biology of toxins 445 29 april...
TRANSCRIPT
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
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
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?
Aflatoxin: Scientific background, control and implications. Goldblatt, Leo A. New York: Academic Press, 1969.
Eaton, D.L. and Gallagher, E.P. 1994. “Mechanisms of Aflatoxin Carcinogenesis.” Annu. Rev. Pharmacol. Toxicol.
Genetics and Physiology of Aspergillus. Smith, John E. and Pateman, John A. London: Academic Press, 1977.
The Genus Aspergillus: From Taxonomy and Genetics to Industrial Application. Powell, Keith A., Renwick, Annabel and Peberdy, John F. New York: Plenum Press, 1994.
Groopman, J.D., Kensler, T.W. 2005. “Role of metabolism and viruses in aflatoxin-induced liver cancer.” Toxicology and Applied Pharmacology. 206(2): 131-137. 34: 135-172.
Ramsdell, Howard S. and Eaton, David L. 1990. “Species Susceptibility to Aflatoxin B1 Carcinogenesis: Compartive Kinetics of Microsomal Biotransformation.” Cancer Research. 50: 615-620.
Raper, Kenneth B. and Fennell, Dorothy I. The Genus Aspergillus. Baltimore: The Williams & Wilkins Company, 1965.
Smela, M.E, Currier, S.S., Bailey, E.A. and Essigmann, J.M. 2001. “The chemistry and biology of aflatoxin B1: from mutational spectromety to carcinogenesis.” Carcinogenesis. 22 (4): 535-545.
Thom, Charles and Raper, Kenneth. A Manual of the Aspergilli. Baltimore: The Williams & Wilkins Company, 1945.
Tiwari, R.P., Dham, C.K., Bhalla, T.C., Saini, S.S., Badehra, D.V. 1985. “Mechanism of Action of Aflatoxin B1 in Bacillus megaterium.” Applied and Environmental Microbiology. 49(4): 904-907.