E module Food Carcinogens and lecture carcinogenicity

22 important questions on E module Food Carcinogens and lecture carcinogenicity

What is the link between diet and cancer?

Some substances in the diet or food patterns contribute to the incidence of cancer

What is a carcinogen?

Any agent that increases the incidence of cancer upon (chronic) exposure

  • divided in genotoxic and non-genotoxic carcinogens
    • based on mechanism of action underlying their contribution to cancer 

What are genotoxic carcinogens?

Substances that can cause direct DNA or chromosomal damage
  • can eventually lead to mutations or alterations in the structure or function of DNA
    • contribute to cancer
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How can genotoxic carcinogens cause DNA / chromosomal damage?

Either:
  • directly
  • after activation by metabolizing enzymes 

What are non-genotoxic carcinogens

Substances that can induce cancer development through mechanisms other than DNA damage

By which mechanisms can non-genotoxic carcinogens cause cancer?

Mechanisms associated with:
  • hormonal effects
  • cytotoxicity
  • cell proliferation
  • epigenetic changes

What are the three main sources of food carcinogens?

  1. carcinogens naturally present in food
    • e.g. from plants
  2. carcinogens formed during processing
    • e.g. during heating of food
  3. carcinogens formed endogenously
    • e.g. formation of nitrosamines in gut due to reaction between nitrite and amines

Due to the DNA damaging properties of genotoxic carcinogens, they are not considered to have a safe level of exposure. Why?

Because each molecule of such a compound is considered to be able to damage DNA and contribute to the multistep process of tumor development

Which approach is used for the qualitative risk management of genotoxic carcinogens?

The MOE approach

Which approach is used for non-genotoxic carcinogens?

  • Tolerable daily intake (TDI) for non-avoidable non-genotoxic carcinogens
  • acceptable daily intake (ADI) for avoidable non-genotoxic carcinogens

Why is it possible to derive a TDI for a non-genotoxic carcinogenic compound?

Because it induces cancer by mechanisms other than damaging DNA directly

What are anticarcinogens in food?

Food components that have a role in prevention of the incidence of cancer

Give examples of classes chemicals associated with anticarcinogenic potential

  1. Vitamins
  2. flavonoids
  3. fibers
  4. polyphenolic compounds 
  5. phytoestrogens
  6. carotenoids
  7. limonene
  8. hydrolysis products of glucosinolates

How many changes are needed for tumor formation?

More than 3 and probably less than 10

What genotoxic carcinogens are there in food? Give examples

1. Naturally present
  • phytotoxins (from plants)
    • alkenylbenzenes (estragole, methyleugenol)
    • pyrrolizidine alkaloids
  • mycotoxins (from fungi/molds)
    • alfatoxin

2. Endogenously formed
  • nitrosamines


3. Formed upon food processing (heating)
  • PAHs: polycyclic aromatic hydrocarbons
  • HCAs: heterocyclic amines (PhIP)
  • acrylamide

Describe the process of endogenously formed genotoxic carcinogens. Give example

Food contains chemicals that are converted in the body, interact with each other and form genotoxic carcinogens

  example: nitrosamines
  • nitrate in veggies are converted into nitrite in the body
  • the nitrate can interact with amines of fish
  • together they form nitrosamines
    • genotoxic carcinogenic 

How are the genotoxic carcinogens Polycyclic Aromatic Hydrocarbons (PAHs) formed?

Pyrolysis of fat
  • temperature 300 - 600 degrees Celsius 

How are the genotoxic carcinogens Acrylamide and PhIP formed?

By maillard reactions of sugars and proteins
  • temperature < 250 degrees Celsius

How are the genotoxic carcinogens furans formed?

By thermal degradation of ascorbic acid, amino acids, carbohydrates, unsaturated fatty acids and carotenoids

  • in coffee, canned and jarred foods  

Which genotoxic carcinogens are of high priority due to their MOE?

  • Pyrrolizidine alkaloids
  • acrylamide
  • aflatoxin B1
  • furan

What are anti-carcinogens in food

Chemicals in food that may reduce cancer formation by various mechanisms

Name the mechanisms by which anti-carcinogens may reduce cancer formation

  • Reduction of effects of carcinogens by modulation of biotransformation enzymes
  • reduction of inflammation
  • reduce oxidative/electrophilic stress
  • reducing proliferative tumor cells
  • reducing bioavailability

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