Flashcards in L20- Carcinogenesis: Causes of Cancer Deck (19):
What is a carcinogen?
Any agent that significantly increases the risk of developing cancer
What are Initiators in terms of carcinogens?
Often Genotoxic i.e. can chemically modify or damage DNA
What are promoters in terms of carcinogens?
Often non-genotoxic e.g. induce proliferation and DNA replication
What is a complete carcinogen?
“complete” carcinogens can initiate and promote e.g. UV light
What is Initiation ?
-Chemical modification of DNA
-Replication of modified DNA and mis-incorporation by DNA polymerase
What can methylation of a CpG site within the promoter region of a gene do?
Can lead to their silencing, a feature found in a number of human cancers (for example the silencing of tumor suppressor genes)
Mutations found in oncogenes can lead to:
a gain of function
Mutations found in Tumour suppressor Genes (TSGs) can lead to:
lead to a loss of function
Metabolic activation of cancer : Direct acting factors works by...
interacting directly with DNA
e.g. oxygen radicals, nitrosomines, UV light, ionising radiation
Metabolic activation of cancer: Procarcinogens are...?
Carcinogens that require enzymatic (metabolic) activation before they react with DNA
e.g. aromatic amines, polycyclic aromatic hydrocarbons (PAHs)
Name the defences against carcinogenesis..
DNA repair enzymes
Apoptotic response to unrepaired genetic damage
Immune response to infection and abnormal cells
What are the Categories of human carcinogens
Chemicals e.g. PAHs, nitrosamines
Infectious agents e.g. human papilloma virus, Helicobacter pylori
Radiation e.g. UV light, radon
Minerals e.g. asbestos, heavy metals
Physiological e.g. oestrogen, androgens
Chronic inflammation – free radicals and growth factors
Target tissue of Aflatoxin?
Target tissue of Asbestos?
Target tissue of X-Rays?
Target tissue of HBV?
Target tissue of HPV?
Why alcohol is a carcinogen?
increases levels of oestrogen and testosterone
increases uptake of carcinogenic chemicals into cells within the upper GI
reduces levels of folate, needed for accurate DNA replication
can kill surface epithelium leading to unscheduled proliferation