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 ID: 931521
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Slide1
You Are What You Eat
CH339K
Slide2Life Rule 1: Nobody gets out alive
Cover of
Science
, Sept. 23, 1983
Slide3Mutagens 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
Slide4Finding 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
Slide5Things 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
Slide6Mutagenic 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 N2Helix distortion causes copy errors – mostly frameshifts
Slide7Heterocyclic amines
Produced in cooked meat and fish from amino acids, sugars, and
creatine
Slide8HAs
mice tumors developed in the
liver ,
forestomach
, lung, blood vessels, hematopoietic system,
and lymphoid
tissue
Slide9HAs (cont.)
Heterocyclic amines
“Standard” carcinogens
Slide10HAs – Metabolic activation
Slide11Natural Pesticides
Safrole
Aflatoxins
Psoralens
Solanines
Pyrollizidines
Others
Slide12Safrole
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
Slide13Aflatoxins
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 b1
Slide14Aflatoxin
Metabolism
Slide15Aflatoxin
Action
Slide16Psoralens
Psoralens
are a class of photo-mutagenic and photo-chemotherapeutic molecules that covalently modify nucleic acids
Iintercalate
into and
photoalkylate
double stranded DNA.
P
rimary targets of
psoralens
are
thymidine
residues
Form both monoadducts and interstrand crosslinksReaction takes place between the 3,4 (pyrone) or 4',5' (furan) double bonds of the psoralen and the 5,6 double bond in pyrimidines .
Slide17Psoralens – DNA cross links
Slide18Psoralens
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
Slide19Solanines
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