Epidemiology of Cancer and Chemical Carcinogenesis

Question 1

80% of neoplasms are caused by what?

Answer 1

Environmental factors

Question 2

Give one example of regional difference in cancer.

Answer 2

Rate of melanoma more prevalent in the southern half of the U.S. and Colorado where exposure to ultraviolet light is higher

Question 3

Give one example of worldwide differences in rates of specific cancer

Answer 3

Esophageal cancer is about 300 times higher in Iran than Nigeria

Question 4

True or False: Second and third generation migrants adopt the cancer risk of the country to which they move.

Answer 4

True

Question 5

Tobacco is responsible for ____% of all cancers

Answer 5

30

Question 6

Cigarette smoke is responsible for ___% of lung carcinoma

Answer 6

85

Question 7

What types of cancer does cigarette smoke cause?

Answer 7

Oral pharynx
Larynx
Esophagus
Pancreas 
Bladder

Question 8

What are the top three leading causes of cancer deaths in males in the US?

Answer 8

Lung 34%
Prostate 12%
Colon/ Rectum 11%

Question 9

What are the top three leading causes of cancer deaths in females in the US?

Answer 9

Lung 21%
Breast 18%
Colon/Rectum 13%

Question 10

What is the lifetime risk of cancer in men in Colorado?

Women

Answer 10

1 in 2

2 in 5

Question 11

What is the most common cancer in men?

Answer 11

Prostate

Question 12

What did Pott do in 1775?

Answer 12

Noted an increased incidence of scrotal cancer among chimney sweeps, attributed it to chronic soot exposure

Question 13

What did Kenneway and Heiger do in 1935?

Answer 13

Identified polycyclic aromatic hydrocarbons as the active carcinogens in coal tar

Question 14

What did Berenblum do in 1941?

Answer 14

Reported croton oil (a plant oil) “promotes” but does not “initiate” skin tumors in rodents

Question 15

Name four environmental carcinogens.

Answer 15

1. Polycyclic aromatic hydrocarbons
2. Aromatic amines
3. Nitrosamines
4. Aflatoxins

*They become carcinogens once metabolized by CYP450

Question 16

Describe polycyclic aromatic hydrocarbons

Answer 16

Formed from incomplete combustion of fossil fuels

Ultimate carcinogen is the diol, epoxide

Question 17

Describe aromatic amines

Answer 17

Used in inductrial and consumer products

N-hydroxylation and sulfation are required

Question 18

Describe nitrosamines

Answer 18

Formed when 2- amines in food react with nitrous acid in the stomach. (Nitrous acid is produced when dietary nitrite, a common food preservative, comes in contact with stomach acid)

Microsomal hydroxylation leads to a carbonium intermediate

Question 19

Describe aflatoxin

Answer 19

Common in moldy grains and ground nuts, especially in the tropics and developing nations where most foods are not refrigerated.

In the US found in moldy corn and wheat

Microsomal epoxidation is required

Question 20

What bacteria produces aflatoxin?

Answer 20

Aspergillus flavus

Question 21

Active metabolites are strong….

a. Neutrophil
b. Electrophil

Answer 21

Electrophil

Question 22

How do electrophils damage cells?

Answer 22

They modify proteins, RNA, and DNA

Question 23

True or False:

All carcinogens need activation by microsomal enzymes

Answer 23

False. Some chemicals are direct carcinogens

Question 24

Name two direct carcinogens.

Answer 24

1. Alkylating agents

2. Acylating agents

Question 25

Attack by electrophilic species to generate modified bases or bulky adducts causes what two kinds of mutations?

Answer 25

Mispairing and Frameshift

Question 26

Name three examples of non-environmental carcinogens

Answer 26

1. Metal vapors
2. Arsenic exposure
3. Thorotrast
   Also…..
   Exposure to vinyl chloride
   Asbestos
   Benzene
   and Radon

Question 27

How does the Ames test work?

Answer 27

Measures the ability of a given chemical to mutagenize a specific strain of Salmonella typhimurium

Question 28

Why is the Salmonella typhimurium used in the Ames test unique?

Answer 28

Because it is genetically altered to have a nonfunctional histamine gene so it can’t synthesize histamine

Question 29

How does an Ames test work?

Answer 29

Place 10^8 His- bacteria on a media plate lacking histamine with a crude fraction of liver enzymes. Place a drop of chemical on and see if bacteria begin to grow

Question 30

Name some foods in which mutagens can be found.

Answer 30

Every good food and figs

Question 31

True or False:

Chemicals are generally dose-dependent in causing cancer

Answer 31

True for the most part

Question 32

True or False:

Specific carcinogens often cause one specific type of cancer

Answer 32

True

Question 33

The greatest risk for developing cancer occurs carcinogens effect which cell population.

Answer 33

stem cells

Question 34

Do fully differentiated cells become malignant?

Answer 34

No

Question 35

What are the two distinct stages of cancer development?

Answer 35

1. Initiation- Irreversible and direct effect of carcinogen

2. Promotion- Reversible; noncarcinogen

Question 36

What are promoters?

Answer 36

They promote cell proliferation

They are often irritants that can cause inflammation

They are not mutagens or carcinogens

Question 37

Name an example of promoters in:

Lung Cancer

Colon Cancer

Answer 37

Phenols in cigarette smoke

Bile salts promote cancer in benign polyps

Question 38

Name three disorders that are characterized by defects in DNA repair activities and are prone to develop cancer at a young age.

Answer 38

Xeroderma pigmentosum

Ataxia-telangiectasis

Fanconi’s anemia

Question 39

Name two epigenetic effects of carcinogens.

Answer 39

1. Carcinogens can covalently modify proteins and RNAs

2. Many chemical carcinogens are toxic to cells