neoplasia 3 Flashcards
what are the intrinsic and extrinsic factors causing cancer
increased frequency of carcinogens mainly due to increasing life span intrinsic factors - age sex (breast) hereditary extrinsic factors- environment lifestyle behaviours (obesity, no physical activity, unhealthy diet, smoking and alcohol)
what are more examples of extrinsic factors that are carcinogens (envinroment)
responsible for 85% of populations cancer risk.
chemicals - asbestos
radiation
infection
however there is often a long delay between cancer and carcinogen exposure. thats why risk of cancer depends on total carcinogen dosage and may be more organ specific e.g balddercancer and 2-napthylamine
what is the sequence in which carcinogens are administered
initiators followed by a prolonged exposure to promoters. the initiators will cause mutations and the promoter will cause prolonged proliferation of these target tissues = monoclonal expansion of the mutated cells.
categories of mutagenic chemical carcinogens and examples
polyaromatic - in cigarette smoke
aromatic amine- in cigarette smoke
N-nitrosocompounds - found in stomach of people who eat a lot of pickled/acidic food
alkylating agents - used in plastic manufactures
natural products- grows on nuts that have been badly stored
what are pro-carcinogens
type of carcinogen that is converted in the liver by p450 to a carcinogen
what are complete carcinogen
carcinogens that act both as initiators and promoters
types of mutagenic radiation
uv light - but does not penetrate deeper than the skin
ionising radiation - including X-rays and nuclear radiation from radioactive elements.
how does radiation affect DNA
indirect DNA damage by free radicals
direct DNA damage by altering bases and single/double stranded breaks
types of exposure to radiation
uv sunlight - v dangerous because daily exposure
ionising - from radon and medical tests e.g X-rays.
how can infections act as carcinogens
some infections affect genes that control cell growth
some affect indirectly y causing chronic tissue injury where regeneration acts as promotor or causes new mutations from DNA replication errors
examples of infections which act as carcinogens
HPV - (cervical cancer) expresses E6 and E7 which inhibit P53 (cell cycle checkpoint) and PRB which are both important in cell proliferation
Hepatitis B and C- cause chronic liver cell injury and regeneration
Helicobacter pylori- gastric inflammation
EBV- burkitts lymphoma
HIV- acts indirectly by lowering immunity and allowing other carcinogenic infections
example of how inherited predisposition to neoplasia can occur
retinoblastoma in members of same family
difference between tumours in family and tumours in general population (2 hit hypothesises)
familial - first hit was through gremlin affected cells in body and second by sporadic mutations - so in reality only 1 hit. much more likely to occur
sporadic- requires 2 somatic mutations in the same cell. much less likely
how initiations and promotion lead to neoplasms when affecting photo-oncogenes and tumour suppressor genes
tumour supressor genes usually inhibit tumour growth. both alleles must be inactivated (2 hits)
genes that enhance neoplastic growth are called oncogenes and are activated promo-oncogenes, only 1 allele needs to activated here.
what is RAS (oncogenes)
RAS protooncogenes encode G protein that relays signals into the cell that eventually push the cell past restriction point. Mutant RAS encodes a protein that is always active producing constant signal to pass through the cell cycles restriction point. this is found in 1/3 of all neoplasms.
