MoD 11 Neoplasia 3 Flashcards
What is cancinogenesis?
causes of cancer
Give examples of some intrinsic and extrinsic factors leading to cancer
Intrinsic- Age, sex (hormonal), heredity
Extrinsic- environment, lifestyle
What are the 5 leading behavioural risks leading to cancer?
High BMI Low fruit and veg intake Lack of physical activity Tobacco use Alcohol use
What 3 main categories do extrinsic carcingoens fall into?
Chemicals
Radiation
Infections
What three things did malignant neoplasms caused by the dye 2-napthylamine show?
Long delay (sometimes decades) between exposure and malignant neoplasm onset Risk of cancer depends on total carcinogen dosage Sometimes organ specificity for particular carcinogens e.g 2-napthylamine causes bladder carcinoma
What did the Ames test show?
That initiators are mutagens while promoters cause prolonged proliferation in target tissues
What kinds of chemicals are initiators (mutagens)?
Polycyclic aromatic hydrocarbons, aromatic amines, N-nitroso compunds, natural products
What is asbestos?
Mutagen originating from a rock which was used industrially due to its fire retardant properties
Inhalation of its needle shaped dust causes cancer as the fibres get into the lung pleura
How are N-nitroso ocmpounds formed?
Stomach converts nitrates in cured and pickled food to these
What are pro-carcinogens?
Chemicals that become carcinogenic when converted to carcinogens by cytochrome P450 enzymes in the liver
What are complete carcinogens?
Carcinogens that act as both initiators and promoters
What types of radiation are mutagenic?
alpha and beta particles
gamma rays
x rays
UV rays
What is ionising radiation?
Radiation that strips electrons from atoms
Includes x rays and nuclear radiation
What comprises nuclear radiation?
Alpha particles, beta particels, gamma rays
In what ways can radiation damage DNA?
Directly by altering bases and causing single/ double strand DNA breaks
indirectly by generating free radicals
How do infections behave carcinogenically?
Directly affect genes that control cell growth
Indirectly by causing chronic tissue injury where resulting regeneration either acts as a promoter for a pre-existing mutations or else causes new mutations from DNA replication errors
How does HPV act as a carcinogen?
Direct carcingoen that expresses E6 and E7 proteins which inhibit p53 and pRB respectively, both of which important in cell proliferation
How do hepatitis viruses act as carcinogens?
Indirectly as cause chronic liver injury and regeneration
How does HIV act as a carcinogen?
Indirectly by lowering immunity so other potentially carcinogenic infections can occur
What is the inheritance pattern of retinoblastoma?
dominant
What is the two hit hypothesis?
Two mutations must occur for a cancer to develop. so in familial cancers one mutation is present in the germ-line so one somatic mutation has to occur for cancer to develop whereas in sporadic cancers, both mutations must be somatic mutations in the same one cell
How do tumour suppressor gene mutations support the two hit hypothesis?
Tumour supressor gene will have two alleles and both these alleles must be hit and inactivated for neoplastic growth to occur
Do both alleles of a proto-oncogene need to be mutated to favour neoplastic growth?
No, just one
What is RAS?
First human oncogene to be discovered
Proto-oncogene for RAS encodes a small G protein that relays signals to push cell past cell cycle restriction point/ Mutant RAS is constantly activated so constantly signals cell past restriction point
