neoplasia 3 + 4 Flashcards
what are extrinsic carcinogens?
- chemicals
- virsues
- radiation
- behaviour (lifestyle factors)
approx 85% of cancers are caused by environment/extrinsic factors
what are intrinsic carcinogens?
- hereditary (e.g. breast cancer)
- chronic inflammation
- age (cells have been exposed to extrinsic carcinogens for longer)
- sex - especially hormones
what lifestyle factors can be controlled to reduce risk of cancers?
- smoking
- maintain healthy weight
- healthy balanced diet
- sun safety
- cut back on alcohol
- being active
the risk of developing cancer increases significantly when multiple of these factors aren’t practiced
2-napthylamine is an industrial carcinogen which was used as a dye in the manufacturing industry.
what did malignant neoplasms caused by 2-napthylamine teach us?
- long delay between carcinogen exposure and malignant neoplasm onset
- risk of cancer depends on total carcinogen dosage
- there is sometime organ specificity for particular carcinogens
what is the difference betwen an initiator carcinogen and a promoter carcinogen?
initiator carcinogen = carcinogens which change DNA sequence due to a mutation
promoter carcinogen = carcinogens which allow for neoplastic clone to form
initiator carcinogen needed first
what is the ames test?
uses bacteria to determine if something can cause a change in DNA sequence by initiating a mutation
if the test is positive then the substance is deemed carcinogenic
what are pro-carcinogens?
pro-carcinogens are converted to carcinogens in the liver by cytochrome P450
how do infections cause cancers?
- Direct - directly affect genes that control cell growth (e.g. HPV)
- Indirect - indirectly causes chronic tissue injury + resulting regeneration acts either as a promoter for pre-existing mutations or cause new mutations from DNA replication errors (e.g. Hep B)
how is HPV associated with cancer?
(important to know this)
associated with cervical carcinoma
* creates 2 proteins E6 + E7
* virus infects the cell, ensures it doesn’t die and then hijack’s its DNA replication machinery to make more viral particles
* E6 inhibits p53 which prevents cells from undergoing apoptosis
* E7 prevents normal functioning of retinoblastoma gene (an important checkpoint in cell cycle)
what are retinoblastomas?
- tumours of the eye
- inherited link - autosomal dominant trait
- caused by mutations in the RB1 gene which is a TSG + is a regulator of the G1/S cell cycle check point
- both eyes affected (especially if its caused by inherited disorders ~40%)
- one eye affected (sparadic in nature ~60%)
what is the 2 hit hypothesis?
for TSG they must have both alleles affected hit 1 = 1st allele hit 2 = 2nd allele
inherited cancers:
* cells already have mutation
* so much easier for hit 1 and 2
sporadic cancers:
* cells need to acquire initial mutation
* then hit 1 + 2 take a lot longer
what is the RAS gene?
- first discovered human oncogene
- most common type of abnormality involving proto-oncogenes in human tumours occurs in the RAS gene
what is the normal function of the RAS gene?
- a growth factor binds to receptor
- RAS acts a proto-oncogene
- RAS binds to GTP which causes conformational changes in RAS making it active
- RAS enters cell and makes cyclin D
- a retinoblastoma (TSG) is phosphorylated
- cells continue to progresses through the G1/S cell cycle checkpoint
how do mutations in RAS and retinoblastomas (TSG) cause uncontrolled cell growth?
mutation in RAS:
* permanently active so growth factor no longer needed for cells to pass through cell cycle
* uncontrolled growth
2 hits on retinoblastoma gene:
* retinoblastomas can’t control the cells passing through the G1/S cell cycle
what is xeroderma pigmentosa?
- autosomal recessive disorder
- mutations in 1/7 genes that affect DNA nucloeitde excision repair
- very sensitive to UV damage as they have no way of repairing damage to DNA
