80% of neoplasms are caused by what?
Environmental factors
Give one example of regional difference in cancer.
Rate of melanoma more prevalent in the southern half of the U.S. and Colorado where exposure to ultraviolet light is higher
Give one example of worldwide differences in rates of specific cancer
Esophageal cancer is about 300 times higher in Iran than Nigeria
True or False: Second and third generation migrants adopt the cancer risk of the country to which they move.
True
Tobacco is responsible for ____% of all cancers
30
Cigarette smoke is responsible for ___% of lung carcinoma
85
What types of cancer does cigarette smoke cause?
Oral pharynx Larynx Esophagus Pancreas Bladder
What are the top three leading causes of cancer deaths in males in the US?
Lung 34%
Prostate 12%
Colon/ Rectum 11%
What are the top three leading causes of cancer deaths in females in the US?
Lung 21%
Breast 18%
Colon/Rectum 13%
What is the lifetime risk of cancer in men in Colorado?
Women
1 in 2
2 in 5
What is the most common cancer in men?
Prostate
What did Pott do in 1775?
Noted an increased incidence of scrotal cancer among chimney sweeps, attributed it to chronic soot exposure
What did Kenneway and Heiger do in 1935?
Identified polycyclic aromatic hydrocarbons as the active carcinogens in coal tar
What did Berenblum do in 1941?
Reported croton oil (a plant oil) “promotes” but does not “initiate” skin tumors in rodents
Name four environmental carcinogens.
- Polycyclic aromatic hydrocarbons
- Aromatic amines
- Nitrosamines
- Aflatoxins
*They become carcinogens once metabolized by CYP450
Describe polycyclic aromatic hydrocarbons
Formed from incomplete combustion of fossil fuels
Ultimate carcinogen is the diol, epoxide
Describe aromatic amines
Used in inductrial and consumer products
N-hydroxylation and sulfation are required
Describe nitrosamines
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
Describe aflatoxin
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
What bacteria produces aflatoxin?
Aspergillus flavus
Active metabolites are strong….
a. Neutrophil
b. Electrophil
Electrophil
How do electrophils damage cells?
They modify proteins, RNA, and DNA
True or False:
All carcinogens need activation by microsomal enzymes
False. Some chemicals are direct carcinogens
Name two direct carcinogens.
- Alkylating agents
2. Acylating agents
Attack by electrophilic species to generate modified bases or bulky adducts causes what two kinds of mutations?
Mispairing and Frameshift
Name three examples of non-environmental carcinogens
- Metal vapors
- Arsenic exposure
- Thorotrast
Also…..
Exposure to vinyl chloride
Asbestos
Benzene
and Radon
How does the Ames test work?
Measures the ability of a given chemical to mutagenize a specific strain of Salmonella typhimurium
Why is the Salmonella typhimurium used in the Ames test unique?
Because it is genetically altered to have a nonfunctional histamine gene so it can’t synthesize histamine
How does an Ames test work?
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
Name some foods in which mutagens can be found.
Every good food and figs
True or False:
Chemicals are generally dose-dependent in causing cancer
True for the most part
True or False:
Specific carcinogens often cause one specific type of cancer
True
The greatest risk for developing cancer occurs carcinogens effect which cell population.
stem cells
Do fully differentiated cells become malignant?
No
What are the two distinct stages of cancer development?
- Initiation- Irreversible and direct effect of carcinogen
2. Promotion- Reversible; noncarcinogen
What are promoters?
They promote cell proliferation
They are often irritants that can cause inflammation
They are not mutagens or carcinogens
Name an example of promoters in:
Lung Cancer
Colon Cancer
Phenols in cigarette smoke
Bile salts promote cancer in benign polyps
Name three disorders that are characterized by defects in DNA repair activities and are prone to develop cancer at a young age.
Xeroderma pigmentosum
Ataxia-telangiectasis
Fanconi’s anemia
Name two epigenetic effects of carcinogens.
- Carcinogens can covalently modify proteins and RNAs
2. Many chemical carcinogens are toxic to cells