Flashcards in 20. Carcinogenesis - causes of cancer Deck (71)
Give some examples of occupational carcinogens
- cadmium and nickel
- radon (mining)
- solvents and preservatives (painters and furniture makers)
- tannins (leather footwear manufacture)
Give examples of chemical carcinogens
Give examples of infectious agents as carcinogens
- H. pylori
Give examples of radiation as a carcinogen
- UV light
Give examples of mineral carcinogens
- heavy metals
Give examples of physiological carcinogens
What are the carcinogens involved in chronic inflammation?
- free radicals
- growth factors
There is a very wide variety of agents implicated in carcinogenesis. What do they all have in common?
Prolonged exposure to each of these agents can lead to the accumulation of genetic alterations in clonal populations of cells
Which organ does aflatoxin target?
Which organs does alcohol target?
Pharynx, larynx, oesophagus, liver
Which organ does asbestos target?
Which organ do X-rays target?
Bone marrow (leukaemia)
Which organ does UV light target?
Which organ does oestrogen target?
Which organs does tobacco smoke target?
Mouth, lung, oesophagus, pancreas, kidney, bladder etc
Which organ does HBV (hepatitis B virus) target?
Which organ does HPV (human papilloma virus) target?
Carcinogen can also by non-genotoxic. What does this mean?
Induce proliferation and DNA replication
What is an INITIATOR?
A carcinogen that can modify or damage DNA (genotoxic)
What is a PROMOTER
A carcinogen that can induce proliferation and DNA replication (non-genotoxic)
What is a "complete" carcinogen?
A carcinogen that can both initiate and promote. eg. UV light
What does mutation induction (initiation) require?
- chemical modification of DNA
- replication of modified DNA and mis-incorporation by DNA polymerase
DNA polymerases make mistakes at a very low but significant rate. What does this result in?
Accumulation of genetic variation or polymorphisms in coding and non-coding sequences in the genome. Some of these changes are deleterious (mutations)
How might chemical modification of the nucleotides involved in base-pairing occur?
Through environmental insult or through the action of endogenous reactive molecules such as free radicals produced by normal physiological processes
Agents that are good promoters contribute to carcinogenesis in 2 important ways. What are they?
- stimulate the 2 rounds of DNA replication required for mutation fixation
- stimulate clonal expansion of mutated cells, which enables the accumulation of further mutations
Give an example to explain the stages of initiation, promotion and progression
- mouse skin tumour model
- genotoxic initiating agent damages DNA
- promoting agents fixes damage as a mutation and converts normal cell into mutated 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
What makes DNA replication a more error-prone process?
DNA replication in the presence of DNA damage is an error-prone process that can result in permanent changes in DNA sequence
Repeated treatment with promoting agents/ exposure to exogenous or endogenous mutagens can result in what?
Gradual accumulation of mutations
Exogenous mutagens are environmental and endogenous mutagens occur naturally within cells. Give examples of the latter
- oxygen radicals
- lipid metabolism byproducts