Session 9 Neoplasia Flashcards
How does carcinogen dosage effect the type of cancer?
Influences onset
Risk depends on total dosage of carcinogen
Sometimes organ specificity for certain carcinogens
How do carcinogens work?
Some chemical carcinogens called initiators, must be given followed by a second class of carcinogens called promoters
Initiators are mutagens
Promoters cause prolonged proliferation in target tissue
What are the classifications of mutagenic chemicals?
- polycyclic aromatic hydrocarbons
- aromatic amines
- N nitroso compounds
- alkylation agents
- diverse natural products
What are carcinogens that act as both initiators and promoters called?
Complete carcinogen
What are pro carcinogens?
Chemicals that are converted to carcinogens by the cytochrome p450 enzyme in the liver
What type of radiation is damaging and how does radiation cause damage?
Ionising radiation = x rays and nuclear.
Generates free radicals
UV increases risk of skin cancer
Ionising radiation damages DNA bases and causes single and double strand DNA breaks
Natural background radiation = radon, main exposure. Risk increases if in a poorly ventilated area.
How is HPV a direct carcinogen and how is HIV an indirect carcinogen?
It expresses genes that inhibit p53 and pRB protein function, both which are important in cell proliferation.
HIV = indirect by lowering immunity and allowing other potentially carcinogenic infections to occur?
How are Hep B and C indirect carcinogens?
Cause chronic liver cell injury and regeneration.
How can someone have a predisposition to neoplasia?
Through germline mutations
Affects all cells of the body, unlike acquired mutations
How many genes need to be inactive to stop tumour suppressor genes?
Both alleles must be inactive
How many alleles of an oncogene need to be active?
One allele
What is RAS and what does a mutated RAS do?
RAS = an oncogene
The proto ongene version of RAS encodes a small GPSR that relays signals into the cell that pushes it pass the restriction point in the cell cycle.
Mutant RAS means that there’s a constant signal to pass through the cell cycles restriction point
What can proto oncogenes encode for?
Growth factors Growth factor receptors e.g HER2 Plasma membrane signal transducers Cell cycle regulators Apoptosis regulators
What is xeroderma pigmentosum (XP)??
An autosomal recessive disease due to mutations in one of 7 genes that affect DNA nucleotide excision repair.
Patients are sensitive to UV damage and can develop skin cancer at a very young age
What’s hereditary non polyposis colon cancer syndrome?
Autosomal dominant, associated with colon carcinoma and the germline mutation affects one of several DNA mismatch repair genes
