Carcinogenesis

Question 1

How does gene-environment interations apply to cancer?

Answer 1

Cancer = disease of aging influenced by environmental, personal and cultural factors superimposed on inherited susceptibility

(GENE-ENVIRONMENT INTERACTIONS)

Question 2

What is a proto-oncogene?

Answer 2

it is non-mutated oncogene

whos function is to promote growth and survival of cells

Question 3

What is an oncogene?

Answer 3

= a gas pedal on a car

a mutated oncogene is like always have the gas pedal “on” or pressed

Oncogenes encode proteins such as: signaling pathways for cell proliferation (EGFR, MAP kinase), transcriptions factors that control the expression of growth promoting genes (c-myc), inhibitors of apoptosis (BCL2)

Question 4

What is a key requirement for cell cycle activation?

Answer 4

Growth factor = mitogen

Leads to changes in gene expression ultimately resulting in cell cycle progression and proliferation.

Question 5

What is a tumor suppressor gene?

Answer 5

= a “brake” on a car

These BLOCK tumor growth by regulating cell cycle and programming cell death

Question 6

How do tumor suppressor genes become a problem?

Answer 6

*You can inherit a mutation and be heterozygous. If you lose this heterozygosity it is considered a second hit, and you are *

Homozygous for inactive alleles.

Question 7

True/False: in 50% of cancers the p53 tumor suppressor gene is lost.

Answer 7

True

IT is involved in cell cycle arrest, apoptosis, inhibition of angiogenesis and metastasis, DNA repair

Question 8

What is the difference between oncogenes and tumor suppressor genes?

Answer 8

Oncogenes >> mutate >> become ACTIVE

Generally resistant to control; Dominant, therefore needs only one allele to be mutagenically activated.

Tumor suppressor genes >> mutate >> become INACTIVE

Unable to perform normal functions; **Recessive, **therefore both alleles must be inactivated.

Question 9

Genotoxicity

Answer 9

• Most chemical carcinogens*
• Examples:*
• **organic: **polycyclic aromatic hydrocarbons, mycotoxins
• **physical: **radiation, asbestos, heavy metals

Question 10

What is the mechanism by which procarcinogens cause cancer?

Answer 10

procarcinogen >> reactive metabolite >> failure or overload of detoxification >>

antigenic congugate >> immune response

OR

DNA damage >> mutation/cancer or cell death

Question 11

True/false: Many of the genes in the
DNA damage response pathway
are tumor suppressor genes

Answer 11

True

Question 12

What’s the difference between mutations to somatic vs. germline

Question 13

How do non-genotoxic carcinogens work?

Answer 13

NO apparent interaction with DNA

• Impact cellular growth
• Increases DNA synthesis, mitosis and cell division
• Inhibit repair/enzyme function (metals)
• Alter chromatin modifications (Ni)
• Alter signaling pathways
• Induce inflammation

•Effective at high concentrations and chronic exposures

Question 14

Give an example of chemicals that inhibit DNA repair

Answer 14

metals

Question 15

Give an example of chemicals that can activate cellular receptors

Answer 15

hydrocarbons

can bind to transcription receptor (similar to estrogen receptor) and turn it on/off

Question 16

Compare initiation vs. promotion

Answer 16

initiation must come FIRST