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Flashcards in Mechanisms of Oncogenesis Deck (43)
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1

What is cancer? 

A group of diseases characterised by: 

  • Abnormal cell division 
  • Tumour formation 
  • Invasion of neighbouring normal tissue 
  • Metastasis to form new tumours at distant sites 

2

What is a carcinoma? 

Cancer derived in epithelial cells 

3

What is a sarcoma? 

Cancer derived from mesoderm cells (bone and muscle) 

4

What is a adenocarcinoma? 

Cancer found in glandular tissue 

5

What is a hallmark of cancer? 

A characteristic that a normal cell has to acquire to become a cancer cell 

6

Provide some examples of hallmarks of cancer cells

  • Sustaining proliferative signalling 
  • Evading growth suppressors 
  • Avoiding immune destruction 
  • Enabling replicative immortality 
  • Tumour-promoting inflammation 
  • Activating invasion and metastasis 
  • Inducing angiogenesis 
  • Genome instabillity and mutation 
  • Resisting cell death 
  • Deregulating cellular genetics 

7

Explain how age can affect cancer? 

  • Accumulation of mutations over time represent the multi-step process which underlies carcinogenesis 
  • Accumulation only occurs in cells if the cells defence mechanism has been evaded (avoided)
    • Many mechanisms exist for blocking carcinogenesis but over burdening the system increases the possibility that cells will escape surveillance 
      • Hence the longer we live = more time for DNA to accumulate and mutations lead to cancers

8

What is the effect of carcinogens on DNA? 

Carcinogens will cause mutations in the DNA 

9

What are the two types of cells that can undergo mutations? 

Which cell type can have more detrimental conquences. 

  • Germline mutation 
  • Somatic cell mutations 

 

10

What are germline mutations? 

What is the consequence of these types of mutations? 

Germline mutations are mutations within the egg and sperm cell 

  • Mutations can be passed onto offspring 
  • Accounts for 5% of all cancer cases
  • Increased risk of developing cancer → however rarely involved in causing immediate cancer 
  • Inheritable mutation 

11

What is the consequence of somatic cell mutations? 

 

 

  • Mutations that affect somatic cells, cant be passed onto offspring 
  • Constitute to almost all mutations in tumour cells 
  • Only one cell needs to be mutated, then cancer initiation is clonal 
  • Tumour cells can evolve; sub-clonal selection allowing a growth advantage = explains heterogeneity of cells in a tumour 

12

How are cell numbers regulated 

Growth, apoptosis and differentiation will regulate cell numbers: 

  • Cells will proliferate and grow 
  • They will differentiate 
  • They will perform a specific function 
  • They will undergo apoptosis 

This pathway will be regulated by lots of different genes 

13

How is the difference between cell proliferation and cell apoptosis affected? 

Mutations which alter the function of normal genes involved in this pathway 

  • Proliferation 
  • Differentiation 
  • Perform function 
  • Apoptosis pathway 

We lose the abillity to regulate the processes involved in controlling cell number and cell number will continue to increase resulting in a clinically detectable tumour 

14

What are genes that have been actived to be oncogenic called? 

Proto-oncogenes 

15

What is an oncogene? 

An oncogene is a proto-oncogene that has been mutated in a way that it leads to signals which will cause uncontrolled growth (i.e. cancer) 

16

What are tumour supressor genes? 

  • Tumour supressor genes will inhibit both growth and tumour formation. 
  • They will act as braking signals during G1 phase of the cell cycle to stop or slow the cell cycle before S phase 

17

What happens if tumour supressor genes are mutated? 

If tumour supressor genes become mutated then the normal brake mechanism will be disabled = uncontrolled growth i.e. cancer 

18

What are the two causes in which tumour cells arise? 

  • Activation of oncogenes 
  • Supression/ Mutations of tumour supressor genes 

19

What are the assumptions made of carcinogenesis? 

  • Requires malignant transformation of a single cell in order to initiate tumourigenesis 
  • Any cell is likely to be transformed as any other of the same type 
  • Once a malignant cell is generated the mean time to tumour detection is generally constant 

20

Summarise the  Models of carcinogenesis 

  • There are 5 models (but non exclusive) 
    • Non-exclusive as you can find compounds in different models 
  • Model 1 = Mutational (chemical carcinogens) 
  • Model 2= Genome instabillity 
  • Model 3 = Non-genotoxic 
  • Model 4 = Darwinian 
  • Model 5 = Tissue Organization 

21

Describe model 1 of carcinogenesis 

  • Cancder is a multi-step process which includes intiation, promotion and progession 
  • Chemical carcinogens will alter any of these processes by inducing irreversible DNA damage (mutations) and act in a genotoxic matter 

22

What are the types of carcinogens? 

  • Chemical 
    • Bulk of the carcinogens 
    • 10 groups: Polycyclic aromatic hydrocarbons, aromatic amines, azo dyes, nitrosamines, carbamates, halogenated compounds, alkylating agents

  • Physical 

    • Radiation (ionizing, ultraviolet) 
    • Abestos 

  • Heritable 

    • Predisposition - (inherited mutations) 

  • Viral 

    • Hep B and Epstein Barr 

23

How do chemicals in smoke cause cancer? 

Four major groups of polycyclic aromatic hydrocarbons, aromatic amines, nitrosamines and alkylating agents found in cigarette smoke will add functional groups onto DNA bases called DNA ADDUCTS 

24

What is the effect of benzo(a)pyrene on DNA? 

  • Benzo(a)pyrene is a polycyclic hydrocarbon found in cigarette smoke 
    • Not itself carcinogenic (a pro-carcinogen) 
  • However it can easily enter cells and will interact with microsomal enzymes forming benzo(a)pyrene epoxide 
    • This has the effect of changing G nucleotides to T within DNA (mutations) 

25

Describe that test can be carried out to determine whether a substance is carcinogenic? 

AMES TEST 

  • Test will determine the mutagenic activity of chemicals through observing if they cause mutations in simple bacteria e.g salmonella strain 

26

How can physical carcinogens cause cancer? 

  • Will impart energy into biological material 
  • By imparting energy it will cause changes in bonding of molecules = biological effects 

27

What is the primary physical agent? 

Radiation 

28

What are the types of radiation which can act as carcinogens? 

Several types of radiation can act as carcinogens 

  • Ionising radiation (X-Rays, nuclear radiation) 
  • UV radiation 

29

What is the effect of radiation on DNA? 

Will cause DNA damage by causing DNA breaks and pyrimidine dimers. 

These can be repaired, however if there is failed repair then it can cause translocations and mutations 

30

Describe heritable carcinogens and how they lead to cancer 

  • An inherited germ-line mutation has an increased risk of developing certain tumours but rarely involved in causing cancer immediately 
  • In most known hereditary malignant syndromes, the elevated cancer risk is due to a mutation of a single gene (monogenic hereditary diseases)
  • The affected genes concerned usually have a controlling function on the cell cycle or the repair of DNA damage

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