Cancer_and_Carcinogens

1. Cancer and Carcinogens
Bisc 312
Simon Fraser University 2004-3
Rick Lee

2. What is cancer?
A general term for more than 100 diseases
characterized by abnormal and uncontrolled
growth of cells.
What cancer is not
Cancer cells are not immortal cells.

3. Cell lifespan
• Typical cells live ~ 40 generations.
• Afterwards, cells build-up excessive genetic
errors that it results in death.
• Cancerous cells live longer, resulting in
greater probability of error accumulation.

4. Cancer Terms
Benign tumor – A non invasive growth with the potential to
become malignant.
Malignant tumor – When a cancerous cells spread to other parts of
the body via the bloodstream/lymph nodes

5. Mutagens vs. Carcinogens
• Mutagens are any substance that cause
alterations in genetic material.
• Does cancer occur without a mutation?
- No
• Does mutation occur without cancer?
- Yes

6. Types of Mutations
• Point Mutations – Replacement of one nucleotide
with another.

7. Types of Mutations
• Frameshift Mutations – Deletion of nucleotide(s).

8. Types of Mutations
• Chromosome deletions
• Thymine dimers – UV light
• Strand breaks – X-rays, ionizing radiation
• DNA adducts – carcinogens
• Oxidized base – oxidizing agents

9. Mutagens vs. Carcinogens
• Carcinogens are compounds that induce serious
mutations to DNA that can lead to cancer.

10. Mutagen Screening:
Ames Test : Salmonella typhimurium
• Reverse mutation test.
• Mutant bacteria that requires histidine to grow.
Mutation is from a single nucleotide.
• Expose bacteria to potential mutagen and
grow on a plate without media.
• Mutagens will randomly reverse the original
mutation, allowing bacteria to grow without
histidine.

11. • If bacteria grow = compound is mutagenic
• If bacteria does not grow = non-mutagenic

12. Common Exposures to Mutagens
and Carcinogens
• Polycyclic aromatic
hydrocarbons (PAH)
- burning fossil fuels
- creosote-soaked wood
(wood pilings)
• Nitrosamines
- Meat preservatives
- Saliva
Why are my hot dogs always pink?

13. Common Carcinogenic Exposures
Benzo[a]pyrene (PAH)
Results from incomplete combustion of
organic compounds. Found in cigarette
smoke, car exhaust, forest fires, food.

14. Heterocyclic Amines (HCA)
Known to cause cancer in animal studies.
Produced from the cooking process of animal tissue
above 180 degrees C. Higher temperatures produce
more HCA  Flame cooked meats
Common Genotoxic Exposures
Bake (350F) = 176 C (exterior only)
Deep fry (400F) = 232 C
Flame BBQ (800F) = 426 C

15. HCA Formation from High
Temperature Cooking

16. Acrylamide
Found to be genotoxic in in vitro tests.
Produced from high temperature cooking of
starchy foods: french fries, potato chips.
Commonly Genotoxic Exposures

17. • Alcohol and Smoking – Synergistic effect.
Common Carcinogen Exposures
- Alcohol dissolves fats in membranes.
- Carcinogens in smoke enters cells more easily
 increases damage potential.
• = carcinogen

18. • Compounds are more
toxic after being
metabolized.
Ex: Benzo[a]pyrene
Bioactivation
• Metabolism occurs
via cyp450’s in Phase
I and Phase II
reactions
(multifunctional
oxidases)

19. Bioactivation Mutagenicity Test

20. Teratogens
• Teratogens are compounds that
are genotoxic only to
developing fetus. Mother is
unaffected.
• Thalidomide – Used as a
sedative to combat nausea in
pregnant women in 1950’s.
• Caused massive developmental
defects through genetic toxicity.

21. Molecular Cancer Progression Model
Looks at the types and secquences of DNA change leading to cancer

22. Clinical Cancer Progression Model
Looks at the cell/tissue morphology, cell growth rate

23. Clinical Cancer Patterns
• Recurrence of cancer often occurs after the
growth has been surgically removed.
• In 70% of recurrence cases, cells will
dediffferentiate to indicate recurrence.
• In 30% of recurrence cases, cells will
appear perfectly normal, then suddenly
become cancerous.

24. Molecular Patterns in Cancer
• Cancer can arise from multiple gene
mutations for:
• DNA repair
• Anchorage dependence
• Growth suppressors
• Growth promoters
• P53 (apoptosis gene)

25. • Specific sequences of gene loss are
commonly (not always) found in cancer.
Molecular Patterns in Cancer
• DNA repair – first
• Anchorage dependence - last
• Growth suppressors - second
• Growth promoters - second
• P53 (apoptosis gene) – first

26. Patterns of Cancer
• Multiple combinations of gene loss can all
result in cancer.
• Cancer at the same site (lung) in two
individuals often have a different molecular
basis.
• No such thing as a universal cure for cancer.

27. Environmental Toxicologists

28. Initiation
• Initiation
• Generates an neoplastic cell
• Chemical + DNA = mutation
– DNA repair
– Apoptosis (cell death)
– Nothing
• Permanent in the genome (mutation is irreversible)
• Gene expression
• A neoplastic cell
Initiation may never develop into cancerous growths

29. Promotion
• Neoplastic cell grows
– Possibly after a latent period
– Slow process,
– Repeated exposures
• Benign tumour
• Dysplasia
• DNA repair mechanisms are damaged. Cells
still appear normal but increased DNA
mutations occur.

30. Progression
• Begins with visible tumour
• Continued alteration of genetic make-up of the
cell
• Invasion to adjacent tissues
• Metastasis to unrelated organs via blood/lymph
• Malignant tumour
• Hyperplasia
• Cells lose ability to communicate chemically with
each other.

31. Other cancer models

32. Problems with research
• Latency 10-20 yr
• No safe dosage
• Satisfying all models
• Cure vs prevention

34. Cure vs. Prevention