Carcinogenicity

Question 1

What is another term for cancer?

Answer 1

Malignant Neoplasia

Question 2

4 hallmarks of cancer

Answer 2

• normal cells are damaged
• abnormal growth of cells
• dysregulation in the proliferation/apoptosis balance
• Multiple changes in gene expression

Question 3

How many Canadians will die of cancer in 2017? How many will develop cancer in their lifetime?

Answer 3

25%, 50% (yikes)

Question 4

Worst causes (2) of obesity?

Answer 4

Tobacco and Obesity

Question 5

True/False? 70%-90% of all cancers have a linkage to environmental and lifestyle factors

Answer 5

True

Question 6

What is a carcinogen?

Answer 6

An agent (physical or chemical) that causes or induces a neoplasm

Question 7

True/False? Carcinogens are not natural substances

Answer 7

False (aflatoxin from certain molds)

Question 8

True/False? Carcinogens require toxication to be a carcinogen

Answer 8

True

Question 9

What was the first recorded case of cancer and when was it recorded?

Answer 9

Edwin Smith Papyrus, 3000 BC (purchased in 1862)

Question 10

When did Hippocrates coin the term “karkinos”

Answer 10

~ 400 BC

Question 11

What was so cool about Paracelsus?

Answer 11

Father of toxicology, 1500s

Question 12

Percival Pott noticed chimney sweeps getting scrotal cancer in what year? When did the Parliament ban chimney sweeping for minors?

Answer 12

1775, 1840

Question 13

Yamagiwa and Ichikawa proved what and when?

Answer 13

1900s, that a chemical could produce cancer (application of coal tar on rabbit ears caused skin cancer)

Question 14

Who determined the carcinogenic component from tar mixtures? When? What was the compound?

Answer 14

Cook, Hewett, and Hieger. 1933, Polycyclic aromatic hydrocarbons (specifically benzo[a]pyrene)

Question 15

What is the IARC and when was it founded?

Answer 15

International Agency for Research on Cancer, 1965

Question 16

What are the 5 classes of carcinogens?

Answer 16

Group 1: carcinogenic to humans (human and animal data strong)
Group 2A: probably carcinogenic to humans (human data suggestive but limited, animal data positive)
Group 2B: possibly carcinogenic to humans (human data weak/limited, animal data positive or limited)
Group 3: Not classifiable as to its carcinogenicity in humans (human data inadequate, animal data inadequate or limited)
Group 4: probably not carcinogenic to humans (human and animal data negative)

Question 17

What are an example of each group of carcinogen?

Answer 17

Group 1: BPA
Group 2A: DDT
Group 2B: Chloroform
Group 3: Caffeine
Group 4: Caprolactam (only one)

Question 18

What are the three types of carcinogen and the 2 subtypes of each?

Answer 18

- Physical 
    Radiation
    Fibres
- Biological
    Viruses
    Toxins
- Chemical
    Genotoxic
    non-Genotoxic

Question 19

What is the main target of a genotoxic carcinogen?

Answer 19

DNA (causes DNA adducts)

Question 20

What are the different types of genotoxic carcinogens?

Answer 20

Direct
- active in parent form
Indirect
- parent drug is procarcinogen, interacts with DNA to form ultimate carcinogen

Question 21

List 4 indirect carcinogens

Answer 21

Aromatic hydrocarbons
Aromatic amines
N-Nitrosamines
Aflatoxin B1

Question 22

List 4 direct carcinogens

Answer 22

Nitrogen Mustard
Methyl methanesulfonate
Bis(chloromethyl) ether
Ethylene Oxide

Question 23

True/False? Non-genotoxic carcinogens do not alter gene expression

Answer 23

False

Question 24

True/False? Genotoxic carcinogens have no threshold dose whereas Non-genotoxic carcinogens do.

Answer 24

True

Question 25

Define the initiation stage of carcinogenesis

Answer 25

Irreversible genetic change
most initiators are genotoxic
"Fixed" when DNA damage is not repaired before DNA synthesis/cell division
Fate of initiated cells:
- Non-dividing state
- Apoptosis
- Proliferation of initiated cell

Question 26

Define the promotion stage of carcinogenesis

Answer 26

Clonal expansion of initiated cells –> lesion
Promoters do not bind DNA but may affect signalling pathways prolonging cell life
REVERSIBLE
Threshold of effect
High tissue specificity

Question 27

Define the progression stage of carcinogenesis

Answer 27

Conversion of bening lesion into neoplastic cancer (malignancy)
May involve add’l genotoxic events = more DNA damage
Autonomous growth achieved, increased invasiveness, ability to metastasize

Question 28

Where does Biotransformation usually occur?

Answer 28

Liver

Question 29

Detoxication creates ____

Answer 29

Less toxic metabolites

Question 30

Toxication creates _____

Answer 30

More toxic metabolites

Question 31

What is a major source of PAH?

Answer 31

Incomplete combustion of organic compounds

Question 32

How does BAP cause adducts?

Answer 32

Toxicated in liver (BPDE), binds DNA, causes lung tumor

Question 33

What kind of cancer is caused by Aflatoxin?

Answer 33

Liver (Hepatocellular carcinomas)

Question 34

What are the main uses of TCE?

Answer 34

General anesthetic
Alternative to ether/chloroform
Dry-clearnin
Extract flavors from plants
Metal degreaser

Question 35

What are Persistent Organic Pollutants?

Answer 35

Dioxins, insoluble in water, TCDD is most toxic

Question 36

True/False? multiple carcinogens can cooperate to form carcinomas

Answer 36

True