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45 Cards in this Set

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Who was the first person to observe that chemicals can be carcinogens?
Percival Pott
What are the 2 main concepts that we think of in Chemical Carcinogenesis?
1. Initiation
2. Promotion
What is Initiation?
DNA damage caused by a carcinogen
What is Promotion?
The action of chemicals/hormones causing clonal proliferation after there has been DNA damage initiating the cancer.
If you give an initiator without giving a promoter in an animal model of carcinogenesis, what will happen?
No tumors will develop.
If you give an initiator followed by repeated applications of promoter at 2week intervals for several months, what will happen?
Tumors will develop
What if you do the same experiment but with an increased time gap between the initiator application and the promotor applications?
Tumors will still develop
What will happen if you apply the promoter first, then the initiator?
Nothing
What will happen if you spread out the time intervals between promoter applications?
Nothing
What are 2 groups of Direct Acting carcinogens?
1. Alkylating agents
2. Acylating agents
What are 3 alkylating agents?
-B-propiolactone
-Anticancer drugs
-DMS
What does B-propiolactone do?
Directly puts a propyl group onto DNA
What does DMS (dimethyl sulfate) do?
Puts a methyl group on DNA
What is an example of an Acylating agent?
1-acetyl-imidazole
How does acetyl-imidazole work?
By depositing an acetyl group on DNA
How are procarcinogens different from Direct Acting Carcinogens?
They require activation
What are some examples of procarcinogens?
-Benzanthracene
-Benzopyrene
-B-naphthylamine
-Benzidine
What is more powerful; direct acting or procarcinogens?
Procarcinogens
What is Aflatoxin B1 and where is it more of a problem?
A product of spoiled fermenting grain; in 3rd world countries where it causes liver cancer.
What carcinogens are in tobacco?
Who knows!? a ton
What type of cancer is arsenic associated with?
-Lung
-Skin
What type of cancer is Asbestos associated with?
-Lung
-Pleura
-GI tract
What type of cancer is Benzene associated with?
Leukemia
Lymphoma
What type of cancer are Be, Cr, Ni, and Ra associated with?
Lung
What type of cancer is Vinyl Chloride associated with?
-Angiosarcoma
-Liver
What is the basic chemical mechanism for how chemical carcinogens cause cancer?
Electrophilic attack
What is the reaction that occurs?
An electron poor carcinogen reacts with an electron rich cell group.
What is an important mechanism for activating procarcinogens?
The cytochrome P450 system in the liver.
What can over-reactive cytochrome P450s dispose some individuals to?
Lung, skin, and bladder cancer
What is BCNU?
Bischlorethylnitrosourea
What do we eat nitrites in?
Meats - preservatives.
What happens in nitrite metabolism when we eat nitrites?
It reacts with stomach acid to form Nitrous acid; that reacts with amines to form Nitroso compounds that have a positive charge and react with guanines.
What is the specific gene target of DMS and propionolactone?
Purines
What gene mutations are associated with Rodent skin cancer?
Ras gene mutations
What carcinogen is associated with liver cancer and p53 mutations?
Aflatoxin (from rotting grain)
What is the Ames test done for?
Testing a carcinogen's ability to mutate bacteria (mutagens)
How was the original Ames test done?
1. Streak S. typhi (His dependent) to a plate with a little histidine on it
2. Apply carcinogen
3. Wait for all the His to get used up, then if any bacteria continue to survive you know they mutated and reverted to being His - nondependent.
How do promotors work?
By promoting the carcinogeneity of the initiator.
Are promotors carcinogenic by themselves?
No
What exactly do promotors promote?
Proliferation and Clonal Expansion
What are 4 general categories of promotors?
-Phorbol esters
-Hormones
-Phenols
-Drugs
How do Phorbol esters work?
By activating protein kinase C
How does Phenobarbital work?
By blocking transforming growth factor
How do the Estrogens work?
By promoting cell proliferation
How do EtOH, EBV, and H. Pylori promote cancer?
By causing inflammation, cell damage, and repair.