Mechanisms Of Oncogenes

Question 1

What is a oncogene?

Answer 1

A proto oncogene that has been mutated in a way that leads to signals that cause uncontrolled growth

Question 2

What is a tumour suppressor gene?

Answer 2

Inhibit both growth and tumour formation

If mutated uncontrolled cell growth would occur

Question 3

What factors can increase the risk of cancer development?

Answer 3

Smoking
Obesity and weight
Alchohol
Hormones
Sun and UV
Infections and HPV
Physical activity
Diet and healthy eating
Inherited genes
Air pollution and radon
Some workplaces

Question 4

What is the age correlations of cancer?

Answer 4

50-74 year olds = 53% of cases

75+ year olds = 36%

Older we live the more likely we are to develop cancer - longer time for DNA to accumulate mutations that may lead to cancer

Question 5

What is cancer?

Answer 5

A group of diseases characterised by:

• abnormal cell proliferation
• tumour formation
• invasion of neighbouring normal tissue
• metastasis to form new tumours at distant sites

Question 6

What are the hallmarks of cancer?

Answer 6

Avoiding immune destruction

Reprogramming energy production

Question 7

How do cancer mutations arise?

Answer 7

Due to exposure to carcinogens

Question 8

What is carcogenesis?

Answer 8

The accumulation of mutations over time

This accumulation only occurs after the cells defence mechanism of DNA repair have been evaded

Question 9

What 2 types of cell can cancer mutations occur in?

Answer 9

Egg/sperm cells
- germaline mutations (inheritable mutation)
- increased risk of developing cancer
- rarely involved in causing cancer immediately

Somatic cells
- almost all mutations in tumour cells
- initiation of the development of cancer is clonal
- non inheritable
- have heterogeneity

Question 10

What are the 5 models of carcinogenesis?

Answer 10

1. Mutational
2. Genome instability
3. Non-genotoxic
4. Darwinian
5. Tissue organisation

Question 11

How do chemical carcinogens work?

Answer 11

Can work in any step of the carcinogenesis process (initiation, promotion and progression)

Exert they’re effects by adding functional groups to DNA bases called DNA adducts

In the majority of instances chemical carcinogens can induce this DNA damage end act in a genotoxic manner

Eg. Coal tar in tobacco contains Benzopyrene which is found in cigarette smoke

Question 12

What are the classes of carcinogens?

Answer 12

Chemical - 4 main groups (aromatic amines, aromatic hydrocarbons, nitrosamines, and alkylating agents)

Physical - radiation, asbestos

Heritable - predisposition

Viral - Hepatitis B, Epstein Barr

Question 13

What are some examples of chemical carcinogens?

Answer 13

Benzene - refined from crude oil

Arsenic - a poison, used in wood preserves

Cadmium and lead - used in batteries

Nickel - protects metals from corrosion

Formaldehyde - mortuaries

Question 14

What’s the purpose of a Ames test?

Answer 14

A test to determine activity of chemicals by observing whether they cause mutations in sample bacteria.

Question 15

Describe how a Ames test is conducted

Answer 15

1. Fat liver extract is separated into a control and test.
2. The possible mutagen is added to the test and then to a agar plate
3. Control added to agar plate
4. They are incubated
5. A high number of revertants suggests the mutagen causes mutations

Question 16

How do physical carcinogens work?

Answer 16

Act by imparting energy into the biological material which causes changes in the biological molecules

Radiation is the primary physical agent (ionising radiation and UV radiation)

Question 17

How do heritable carcinogens work?

Answer 17

5% of all cancer

The elevated cancer risk is due to a mutation of s single gene

Affected genes usually have a control function in the cell cycle - deficiency in DNA repair would cause more DNA damages to accumulate and increase risk for cancer.

Question 18

What are examples of hereditary carcinogens?

Answer 18

Ataxia telangiectasia
- neuromotor disfunction, dilation of blood vessels
- mutation in ATM gene that codes for serine/threonine kinase (eventually causes cell cycle arrest)
- cancer predisposition: breast cancer, leukaemia, lymphoma

Blooms syndrome
- short stature, rarely exceed 5ft
- mutation in BLM gene which maintains structure of DNA
- cancer predisposition: skin cancer, basal cell/squirmous carcinoma

Lynch type:
- doesn’t have any symptoms
- mutation in DNA mismatch repair genes (MMR)
- cancer predisposition: colorectal cancer

Question 19

How do infectious agents act as carcinogens?

Answer 19

On some occasions viruses can infect a host cell and turn it into a tumour cell.

The tumour cell then divides and a tumour forms

Question 20

What are the properties of tumourogenic viruses?

Answer 20

Stable association with cells

Must not kill cells

Must evade immune surveillance of infected cells - immune suppression

Question 21

What are 2 examples of viruses associated with human cancer?

Answer 21

DNA viruses
- hepatitis B and C
- papilloma viruses

RNA retroviruses
- HTLV-1 (Adult T cell leukaemia)

Question 22

Describe model 2 (Genome instability)

Answer 22

At least 2 events (mutations) are necessary for carcinogenesis and that the cell with the first event must survive in the tissue long enough to sustain a second event.

Question 23

Describe model 3 (non genotoxic)

Answer 23

Several important modulators of cancer risk (diet, obesity) do not seem to act through a structural change in DNA rather a functional change including epigenetic effects.

Question 24

Describe model 4 (Darwinian)

Answer 24

Carcinogenesis by mutation and selection model of clonal expansion

The role of the environment in selecting cells that have some acquired advantage - chemotherapy

Question 25

Describe model 5 (tissue organisation)

Answer 25

What are the 2 main theories of carcinogenesis
- Somatic mutation theory (SMT)
- tissue organisation theory (TOFT)

Question 26

Describe the somatic mutation theory (SMT)

Answer 26

Cancer is derived from a single somatic cell due to multiple DNA mutations

These mutations damage the genes controlling cell proliferation and cell cycle

Neoplasticism lesions are the results of DNA level events

(SINGLE CATASTROPHIC EVENT TRIGGERING CARCINOGENESIS)

Question 27

Describe the tissue organisation field theory (TOFT)

Answer 27

Carcinogenesis is primarily a problem of tissue organisation

Carcinogenic agents destroy the normal tissue architecture thus distrusting cell to cell signalling + compromising genetic integrity

The DNA mutations are random and the effect, not the cause, of tissue level events

(CARCINOGENESIS AS GENERAL DETERIORATION OF THE TISSUE MICROENVIORMENT DUE TO EXTRACELLULAR CAUSES)

Question 28

What will the immune system do in response to cancer?

Answer 28

Protect from virus induced tumours

Eliminate pathogens

Identify and eliminate tumour cells

Question 29

What are the 3 Es of cancer Immunoediting?

Answer 29

Elimination:
- immune system is able to eradicate all tumours

Equilibrium
- when incomplete removal and tumour cells remain dominant and enter equilibrium

Escape
- expanding tumour population becomes clinically detectable