MoD 10 Neoplasia III Flashcards
What are the behaviour habits that increase the risk of developing cancers?
- high BMI
- low intake of fruit and vegetables
- alcohol consumption
- smoking cigarettes (tobacco)
- lack of exercise.
2-naphthylamine is banned industrial dye that was used previously. What key things did we learn from this chemical?
Time delay
- there is a time delay (can be decades) between the exposure to the carcinogen and developing the cancer.
Dose
- the risk of cancer is dose dependent
- increase the dose (exposure) increases the risk.
Specificity
- some carcinogens have effects on certain tissues and organs.
What are ‘complete carcinogens’
These are carcinogens that act as both the initiator and promotor.
What are initiators and promotors and what is the result of these?
Initiators are chemicals that cause DNA mutations
Promotors are chemicals that cause proliferation of cells
When promotors cause proliferation of mutated cells, there is ‘monoclonal expansion’ of this cell
Another way to remember is:
Initiator + promotor = monoclonal expansion.
What are pre-carcinogens and how do they become carcinogens?
These are chemicals that are NOT carcinogenic however upon activation they can be carcinogenic.
They are activated by the CYP450 enzymes in the liver.
Discuss radiation and its potential to be carcinogenic.
Radiation can create free radicals, which indirectly damages DNA.
UV
- most dangerous as constantly exposed to by the sunlight
- only penetrates the skin
- increased risk of skin cancer
Ionising
- strips electrons off atoms
- can cause single or double strand breaks in DNA.
- X-rays, nuclear radiation
- radon is the biggest threat as its seeping from the earth crust.
How do some infections act as direct carcinogens whilst others act as indirect carcinogens ?
Direct
- directly affect genes that control cell growth
Indirect
- cause chronic tissue injury which results in regeneration
- regeneration can cause proliferation of existing mutation
- here, the infection causes promotor like effects
- regeneration can cause new mutations as a result of cell proliferation
- here, the infection causes initiator like effects.
Explain how the Human Papillomavirus (HPV) can be carcinogenic and whether this is a direct or indirect effect?
Direct.
Produces E6 and E7 proteins
- this inhibit p53 and pRB respectively.
- p53 causes apoptosis in cells so inhibiting p53 resists apoptosis
- Rb prevents progression past the restriction point in G1
- it inhibits cell proliferation by inhibiting the cell cycle
Inhibiting p53 and Rb therefore allows the cell to resist apoptosis whilst also allowing uncontrolled cell proliferation.
How does Hep B/C increase the risk of cancer
- chronic injury, inflammation and regeneration of liver tissue
- regeneration means cell proliferation so an existing mutation could be proliferated or a new mutation occurring as a result of proliferation.
This is an indirect effect.
- regeneration means cell proliferation so an existing mutation could be proliferated or a new mutation occurring as a result of proliferation.
How does HIV indirectly increase the risk of cancer?
Compromises immunity therefore increases the chance for carcinogenic infections to take hold and possibly cause cancers.
What did Knudson postulate?
There is a ‘2 hit’ process in cancers
- both alleles for tumour suppressor genes need to be inactivated
He postulated that in familial cancers (eg retinoblastoma), the first mutation occurs in the germline cells whilst the second was in the somatic cells.
In sporadic retinoblastoma, the 2 hits took place in somatic cells which is why it takes longer to develop.
Explain the opposing roles of tumour suppressor genes and proto oncogenes in carcinogenesis, particularly describing the role of Ras.
TSGs prevent tumour formation whilst abnormal activation of the proto oncogenes can cause tumour formation.
Ras
- first oncogene discovered
- it’s proto oncogene coded for a small G-protein that would phosphorylate Rb, which then allowed progression through the cell cycle - allows progression past the restriction point.
- abnormal activation of Ras would keep the small G-protein always on, therefore unrestricted cell cycle progression.
- Rb inhibits past the restriction point if needed so inactivation of this also allows the cell progression past restriction point.
What would inactivating Rb and activation of Ras have on a cells progression though the cell cycle?
It would allow the cell cycle to progress as there is nothing to regulate it.
Name 3 different types of mutations that can occur in genes for DNA repair mechanisms, and name an associated disease with each one.
DNA Nucleotide Excision Repair (NER)
- xeroderma pigmentosum
- autosomal recessive
DNA mismatch repair
- Hereditary Non-Polyposis Colonic Cancer
- autosomal dominant
Repairing DNA double stranded breaks (BRCA 1 & BRCA 2)
- familial breast carcinoma
What is progression and how long does it take?
Progression is the accumulation of DNA mutations in TSGs and proto oncogenes over a number of years, even decades.
The number of mutations occurring is unknown but thought to be below 10.
