Carcinogenesis Flashcards
what are the main categories of carcinogens.
chemicals infectious agents radiation minerals Physiological chronic inflammation
what is the target organ for aflatoxin
liver
what are the target organs for alcohol
pharynx, larynx, oesophagus and liver.
what is the target organ for asbestos
lungs pleura
what is the target organ for X-rays
bone marrow (leukaemia
what is the target organ for UV light
skin
what is the target organ for oestrogen
breast
what is the target organ for tobacco smoke
mouth, lung, oesophagus, pancreas, kidney and bladder.
what is the target organ for HBV
liver
what is the target organs for HPV
Cervix
define carcinogen
any agent that significantly increases the risk of developing cancer
what are the 2 types of biochemical carcinogens
Initiators- genotoxic
promoter- non genotoxic
define a initiator carcinogen
genotoxic i.e. can chemically modify or damage DNA
define a promoter carcinogen
non-genotoxic e.g. induce proliferation and DNA replication
how many rounds of cell division are required to show a initiator has been successful in modifying DNA which has been fives by DNA polymerase.
2
what are the 2 methods of action by which promoters work
Firstly, they can stimulate the two rounds of DNA replication required for mutation fixation
Secondly, they can stimulate clonal expansion of mutated cells, which enables the accumulation of further mutations
how many mutations are required to drive cancer cells
2-8.
describe the full pathogenesis of initiator and promoters and how they work together to cause cancer
- Genotoxic initiating agent damages DNA
- Promoting agent fixes damage as a mutation and converts normal cell into mutant initiated cell
- Promoting agent stimulates clonal expansion of initiated cell to produce papillomas
- Further rounds of mutations and clonal expansion allows papilloma to progress to carcinoma
abnormal methylation of genera promoters leads to epigenetic inactivation of which class of genes
tumour suppressor genes.
CpG islands in promoter sites are methylated then the gene will no longer be expressed.
do mutations in oncogenes lead to gain or loss in function
gain
do mutations in tumour suppressor genes lead to gain or loss in function
loss
the metabolic activation of carcinogens can be from 2 processes, theses include
direct acting-interact directly with DNA.
Pro carcinogen- require enzymatic (metabolic) activation before they react with DNA,
examples of direct acting carcinogens include
oxygen radicals, nitrosomines, UV light and ionising radiation
examples of pro carcinogens
aromatic amines, polycyclic aromatic hydrocarbons
are most carcinogens direct acting or pro carcinogens
procarcinogens
what is the function of the enzymes that help metabolically active pro carcinogens.
enzymes normally function in the detoxification and excretion of toxic chemicals.
how does the involvement of enzymes that normally function in the detoxification and excretion of toxic chemicals introduce a genetic influence on the extent to which we are sensitive to genotoxic attack by different agents
people who activate a particular chemical more efficiently are more likely to get cancer, while those that excrete the activated chemical less efficiently are also more likely to get cancer
does benzopyrene need metabolic activation before it can interact with DNA
Yes
where is benzopyrene obtained
combustion of most organic material such as meat, tobacco and fuel,
what gene does benzopyrene cause mutations in (tumour suppressor gene) and what cancer is it associated with
TP53
Lung cancer.
how do genetic polymorphisms affect susceptibility to carcinogenic exposure
Genetic polymorphisms in genes encoding metabolic activation, detoxifying, or DNA repair enzymes may confer greater or lesser susceptibility to the effects of carcinogenic exposure
what are the main defences against carcinogenic agents
dietary antioxidants detoxification mechanisms DNA repair enzymes Apoptotic response to unprepared genetic damage. immune response to abnormal organism
how many identifies carcinogens are there in tobacco smoke
19 polycyclic aromatic hydrocarbons acrolein nitrosamines radioactive lead and polonium heavy metal- cadmium and chromium.
the conversion of alcohol to what molecule increases the risk of DNA damage
acetylaldehyde.
what hormone levels do alcohol consumption increase which act as promoters
osetrogen and testosterone
is alcohol consumption ncreases uptake of carcinogenic chemicals into cells within the upper GI
reduces levels of what needed for DNA replication
folate
In breast cancer how does oestrogen act as both a promoter and initiator.
Oestrogen binds to transcription factors, which increase proliferation.
Oestrogen converts to estradiol, 3-4 quionne which damages DNA
does menarche decrease or increase your risk of breast cancer
decrease- less and less oestrogen.
what procedure significantly reduced the risk of breast cancer
Oopherectomy
how can chronic inflammatory response result in promoters and imitators being activated
DNA damage from release of free radicals by immune cells - initiation
Growth factor induced cell division to repair tissue damage - promotion
what key cell links tumour cells and inflammatory response
tumour-associated macrophages (TAMs)
what activates tumour-associated macrophages (TAMs)
cytokines released by tumour cells
what do tumour-associated macrophages (TAMs) produce
tumour necrosis factor-alpha (TNF-α), a cytokine that induces and maintains the inflammatory response.
release reactive oxygen and nitrogen species (ROS and RNS) that can act as complete carcinogens, resulting in mutation by damaging DNA and stimulating proliferative through induction of growth factors
ROS - can also induce fibroblasts to undergo autophagy, which releases important nutrients that tumour cells can “feed” on
