Toxicity of Charbroiled Meats: Heterocyclic Amines

1
Toxicity of Charbroiled Meats Heterocyclic
Amines
Laura Metrailler Laura McNabb Nonita
Campbell Courtney Forbes
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How Charbroiled Meats are Toxic

• Cooking certain meats at high temperatures
  creates chemicals that are not present in
  uncooked meats
• A few of these chemicals may cause cancer
• Heterocyclic amines (HCAs) are carcinogenic
  chemicals formed from the cooking of muscle meats

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How are Heterocyclic Amines(HCAs) Formed?

• Optimal conditions for HCA formation
• Longer cooking times
• High temperatures (between 150C and 200C)
• Greater external charring barbecuing, grilling,
  pan-frying

• Meats cooked above a heat source contain the
  highest levels of PAHs because they are exposed
  to smoke formed from the pyrolysis of fatty
  juices that drip down onto the heat source
• Most concentrated in meat juices

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Heterocyclic Amines (HCAs)

• Exposure through diets containing meats cooked at
  high temperature
• Produced during pyrolysis of creatine, amino
  acids proteins
• Mutagenic/carcinogenic
• 17 different HCAs may pose human cancer risk
• Major subclass of HCAs found in the human diet
  are the aminoimidazoazaarenes (AIAs)

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Chemical structures of several AIA-type HCAs

• All AIAs except DiMeIQx are carcinogenic in
  animals
• PhIP is the most abundant compound of the AIA
  group found in fried and broiled meat
• AIAs are present in cooked muscle meats at
  concentrations of parts per billion

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Pathways of AIA metabolic activation leading to
DNA adduct formation

• AIAs PRO-carcinogens
• AIAs must be metabolically activated in order to
  form DNA adducts

• How are AIAs activated?
• Phase I N-hydroxylation catalyzed by hepatic
  cytochrome P450s, forming N-hydroxylamines
• Phase II esterfication of the N-hydroxylamine
  metabolite to form reactive ester derivatives
• The reactive ester derivatives are then able to
  covalently modify DNA

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Structures of AIA-DNA adducts

• Esters generated by phase II metabolism are
  transient metabolites that react with
  nucleophilic sites in DNA
• Ester moieties serve as leaving groups that give
  rise to electrophilic arylnitrenium ion
  intermediates
• Arylnitrenium ions and their resonance forms
  react with particular sites on DNA give rise to
  specific DNA adducts
• The reactive free radicals cause DNA adducts,
  mutations, chromosomal abnormalities, and cancer
  in multiple tissues

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Detoxification Pathway
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Differences in response to HCAs

• Human differences in response to the internal
  exposure of HCAs depends on two major factors

• Individual genotypic differences in the
  activities of the Phase I and Phase II enzymes
• Dietary modulation of the enzyme levels by
  natural inducers or inhibitors found in our food
• Inducing UGT may lead to decreased levels of
  adducts formed through increased detoxification

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Cancer risk associated with method of cooking meat

• Link between individuals with stomach cancer
  consumption of cooked meats
• Researchers assessed diets cooking habits of
  176 people diagnosed with stomach cancer and 503
  people without cancer
• Those who ate their beef medium-well or well-done
  had more than three times the risk of stomach
  cancer than those who ate their beef rare or
  medium-rare
• People who ate beef gt4 x/week had more than twice
  the risk of stomach cancer than those consuming
  beef less frequently
• Additional studies have shown that an increased
  risk of developing colorectal, pancreatic, and
  breast cancer is associated with high intakes of
  well-done, fried, or barbequed meats

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How to reduce exposure to HCAs

• Pay close attention to food preparation methods
  and include foods in your diet that either adsorb
  the HCAs or change their metabolic pathways to
  favor detoxification
• Dont cook food to well-done stage
• Cook meat at lower temperatures (below 200 C)
• Cook meat slowly and for a longer period of time
• Pre-microwaving meat releases HCA precursors
• Marinating and flipping meat reduce the surface
  temperature of the meat, which helps lower HCA
  formation
• Beans and pasta adsorb HCAs before they are
  bioactivated

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Conclusions

• Maximum daily intake of HCAs in food has not been
  established
• No good measure of how much HCAs would have to be
  eaten to increase cancer risk
• No guidelines concerning consumption of foods
  with HCAs
• Further research is needed before such
  recommendations can be made
• Concerned individuals can reduce exposure to HCAs

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Summary

• Heterocyclic amines (HCAs) are formed from the
  cooking of muscle meats
• Four factors influence HCA formation type of
  food, cooking method, temperature, and time
• Major subclass of HCAs found in the human diet
  are the aminoimidazoazaarenes (AIAs)
• AIAs are activated through phase I
  N-hydroxylation and phase II esterfication the
  reactive derivative formed can covalently bind to
  DNA
• N-hydroxy intermediates can be detoxified through
  UGT
• Several studies have shown that charbroiled meats
  can increase the risk of stomach, colorectal,
  pancreatic and breast cancer
• There are several ways that exposure to HCAs can
  be reduced

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References

• Herman A.J. Schut and Elizabeth G. Snyderwine.
  Review DNA adducts of heterocyclic amine food
  mutagens implications for mutagenesis and
  carcinogenesis. Carcinogenesis, Vol. 20, No. 3,
  353-368, March 1999
• National Cancer Institute Factsheet
  Heterocyclic Amines in Cooked Meats.
  http//www.cancer.gov/cancertopics/factsheet/Risk/
  heterocyclic-amines
• James S. Felton and Michael A. Malfatti.
  Supplement Biomarkers as Indicators of Cancer
  Risk Reduction Following Dietary Manipulation
  What Do Diet-Induced Changes in Phase I and II
  Enzymes Tell Us about Prevention from Exposure to
  Heterocyclic Amines? J. Nutr. 1362683S-2684S,
  October 2006 http//jn.nutrition.org/cgi/content/f
  ull/136/10/2683S
• Human Exposure to Heterocyclic Amine Food
  Mutagens/Carcinogens Relevance to Breast Cancer.
  James S. Felton, Mark G. Knize,Cynthi a P.
  Salmon,Michae l A. Malfatti, and Kristen S. Kulp.
  Environmental and Molecular Mutagenesis
  39112118 (2002)