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Flashcards in Causes of cancer Deck (53)
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What are the 5 ways of identifying human carcinogens?

1) Geographical variation in risk - studies in migrant populations
2) Occupational exposure
3) Accidental exposure
4) Big epidemiological surveys
5) Laboratory experiments


What are the categories of carcinogens? 6

1) Chemicals eg. PAHs, nitrosamines
2) Infectious agents eg. HPV, H pylori
3) Radiation eg. UV light, radon
4) Minerals eg. asbestos, heavy metals
5) Physiological eg. oestrogen, androgens
6) Chronic inflammation - free radicals and growth factors


Aflatoxin targets what tissue?



Alcohol targets what 4 tissues?

Pharynx, larynx, oesophagus, liver


Asbestos targets what tissue?

Lung pleura


X-rays target what tissue?

Bone marrow (leukaemia)


UV light targets what tissue?



Oestrogen targets what tissue?



Tobacco smoke targets what 6 tissues?

Mouth, lung, oesophagus, pancreas, kidney, bladder etc.


HBV targets what tissue?



HPV targets which tissue?



What is meant by the term carcinogen?

Any agent that significantly increases the risk of developing cancer


What is the difference between initiator, promotor and complete carcinogens?

Initiators are genotoxic i.e. can chemical modify or damage DNA
Promotors are non genetic and induce proliferation and DNA replication
Complete carcinogens can do both


Name a complete carcinogen?

UV light


What 2 things does mutation indiction (initiation) require?

Chemical modification of DNA
Replication of modified DNA and mis-incorporation by DNA polymerase - requires 2 rounds of replication for a mutations to be fixed


The presence of what in the DNA exacerbates the tendency of polymerase to make mistakes?

Chemical modifications - miscoding or non-coding adducts or lesions


In which 2 ways do promotor carcinogens contribute to carcinogenesis?

1) They can stimulate the 2 rounds of DNA replication required for mutation fixation
2) Secondly they can stimulate clonal expansion of mutated cells, which enables the accumulation of further mutations


Why is clonal expansion of a cell with 1 mutation so important in carcinogenesis?

To form a malignant cell need 2-8 specific mutations, very hard for a cell to acquire these without significant clonal expansion


Give 2 examples of endogenous mutagens?

1) Oxygen radicals
2) Lipid metabolism byproducts


Describe the process of initiation, promotion and progression using a mouse model skin tumour?

1) Genotoxic initiating agent damages DNA
2) Promoting agent fixes the damage as a mutation and converts normal calls into mutant initiated cell
3) Promoting agent stimulates clonal expansion of initiated cells to produce papillomas
4) Further rounds of mutations and clonal expansion allows papilloma to progress to carcinoma


Give the 7 common genetic abnormalities?

1) Base pair substitution
2) Frameshift
3) Deletion
4) Gene amplification (having up to a hundred copies of a gene it would normally only have 2 copies of)
5) Chromosomal translocation
6) Chromosomal inversion
7) Aneuploidy


What is meant by a TSG?

Tumour suppressor gene


What is the most common TSG inactivation event?

Abberant methylation of gene promotor


What is meant by CpG islands and what role do they have in TSG inactivation?

Approximately 70% of genes have CpG islands associated with their promoter sequence, CpG methylation is only effective in shutting down the expression of a gene if it occurs within the promotor sequence of the gene - this is how TSGs are inactivated


Give 4 mutations that occur in oncogenes?

1) Base pair substitutions
2) Amplification
3) Translocation eg. proto-oncogene moved to an area where the genes are more frequently expressed thus ends up expressed more frequently to
4) Inversions


What do mutations in oncogenes lead to?

A gain of function


What do mutations in TSGs lead to?

Loss of function


Give 7 types of mutation which can occur in TSGs?

1) Base pair substitutions
2) Frameshifts
3) Deletions
4) Insertions
5) Chromosomal rearrangements
6) Chromosome loss
7) Promoter methylation


What is meant by a direct activating carcinogen? Give 4 examples.

Interact directly with DNA:
1) Oxygen radicals
2) Nitrosamines
3) UV light
4) Ionising radiation


What is meant by a procarcinogen?

Carcinogens which require enzymatic (metabolic) activation before they react with DNA, though not yet carcinogenic they are often toxic and its the enzymes that normally function in the detoxification and excretion of toxic chemicals which are normally implicated in their activation