Download You Are What You Eat

You Are What You Eat
CH339K
Life Rule 1: Nobody gets out alive
Cover of Science, Sept. 23, 1983
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
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
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 benzo[a]pyrene-7,8-diol-9,10-epoxide
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
Heterocyclic amines
• Produced in cooked meat and fish from amino
acids, sugars, and creatine
HAs
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mice tumors developed in the liver , forestomach, lung, blood vessels,
hematopoietic system, and lymphoid tissue
HAs (cont.)
Heterocyclic amines
“Standard” carcinogens
HAs – Metabolic activation
Natural Pesticides
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Safrole
Aflatoxins
Psoralens
Solanines
Pyrollizidines
Others
Safrole
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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
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
Aflatoxin Metabolism
Aflatoxin
Action
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 .
Psoralens – DNA cross links
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
Solanines
15 mg per 200g potato
Most concentrated in green layer under skin
Cholinesterase inhibitors
Teratogens (cause birth defects)
Amounys increase in diseased potatos
> 40 mg/200g considered toxic