You Are What You Eat

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You Are What You Eat

• CH339K

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Life Rule 1 Nobody gets out alive
Cover of Science, Sept. 23, 1983
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Mutagens and Carcinogens

• Mutagens cause mutations in the DNA genome
• Carcinogens increase the cancer rate in a given
  organism
• Vast majority of carcinogens are mutagens
• Not all mutagens are necessarily carcinogenic
• Carcinogenesis analysis requires animal studies
• Mutagens can be detected more simply and much
  less expensively
• Restrict carcinogenesis testing to known mutagens

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Finding Mutagens the Ames Test

• Named for Bruce Ames, at UC Berkely
• Uses Salmonella typhimurium that has defective
  histidine anabolism
• Strains are used with both point mutations and
  frameshift mutations in histidine synthesis genes
• Rat liver extracts are added to the chemical
  being studied to mimic bodily metabolism
• BECAUSE the actual mutagen may not be the
  chemical itself, but a metabolic product

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Things we put into our food

• Cooking your meat over open flame or in a smoker
  (or using liquid smoke) produces polyaromatic
  hydrocarbons (PAHs)

• Cooking your meat over open flame or in a smoker
  (or using liquid smoke) produces polyaromatic
  hydrocarbons (PAHs)
• Benzo(A)pyrene is metabolized to
  benzoapyrene-7,8-diol-9,10-epoxide

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Mutagenic action

• Benzo(a)pyrene and its epoxide are intercalators
• Intercalating agents stack between the bases of a
  DNA double helix
• The epoxide also formas a covalent bond with G
  residues at N2
• Helix distortion causes copy errors mostly
  frameshifts

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Heterocyclic amines

• Produced in cooked meat and fish from amino
  acids, sugars, and creatine

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HAs

• mice tumors developed in the liver , forestomach,
  lung, blood vessels, hematopoietic system, and
  lymphoid tissue

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HAs (cont.)
Heterocyclic amines
Standard carcinogens
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HAs Metabolic activation
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Natural Pesticides

• Safrole
• Aflatoxins
• Psoralens
• Solanines
• Pyrollizidines
• Others

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Safrole

• Sassafras oil
• Banned in USA from foods and skin products
• Formerly an ingredient of natural root beers
• Metabolized to 1-hydroxysafrole
• Binds to both DNA and proteins
• Induces liver tumors

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Aflatoxins
Aflatoxin b1

• Produced by Aspergillus molds
• Common contaminant of corn, grain, nuts, peanut
  butter, bread, cheese, fruit, and apple juice
• Paricularly concentrated in organic peanut butter
• Both toxic and carcinogenic

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Aflatoxin Metabolism
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Aflatoxin Action
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Psoralens
Psoralens are a class of photo-mutagenic and
photo-chemotherapeutic molecules that covalently
modify nucleic acids Iintercalate into and
photoalkylate double stranded DNA. Primary
targets of psoralens are thymidine residues Form
both monoadducts and interstrand
crosslinks Reaction takes place between the 3,4
(pyrone) or 4',5' (furan) double bonds of the
psoralen and the 5,6 double bond in pyrimidines .
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Psoralens DNA cross links
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Psoralens

• Celery contains up to 100ug/100g
• Stressed celery can contain 100x that amount
• Celery pickers frequently develop skin rashes as
  an occupational hazard
• Interestingly, they are also used to treat a
  variety of skin diseases

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Solanines
15 mg per 200g potato Most concentrated in green
layer under skin Cholinesterase
inhibitors Teratogens (cause birth
defects) Amounys increase in diseased potatos gt
40 mg/200g considered toxic