carcinogenesis

Question 1

what is a carcinogen?

Answer 1

any agent that significantly increases the risk of developing cancer

Question 2

what is the role of promotion in carcinogenesis?

Answer 2

it stimulates DNA replication for mutation fixation

it also stimulates clonal expansion of mutated cells which enables accumulation of further mutations

Question 3

what are the common genetic abnormalities that can lead to cancer

Answer 3

base pair substitution 
chromosomal translocation 
frameshift 
deletion/insertion 
gene amplification 
chromosomal inversion 
aneuploidy

Question 4

what are the categories of human carcinogens

Answer 4

• Chemicals e.g. PAHs, nitrosamines
• Infectious agents e.g. human papilloma virus, Helicobacter pylori
• Radiation e.g. UV light, radon
• Minerals e.g. asbestos, heavy metals
• Physiological e.g. oestrogen, androgens

Question 5

What are the 5 ways of identifying human carcinogens?

Answer 5

1) Geographical variation in risk - studies in migrant populations
2) Occupational exposure
3) Accidental exposure
4) Big epidemiological surveys
5) Laboratory experiments

Question 6

Aflatoxin targets what tissue?

Answer 6

liver

Question 7

Alcohol targets what 4 tissues?

Answer 7

Pharynx, larynx, oesophagus, liver

Question 8

asbestos targets which tissue?

Answer 8

lung pleura

Question 9

xray targets which tissue?

Answer 9

bone marrow

Question 10

Tobacco smoke targets what 6 tissues?

Answer 10

Mouth, lung, oesophagus, pancreas, kidney, bladder etc.

Question 11

HBV targets what tissue?

Answer 11

liver

Question 12

hpv targets which tissue?

Answer 12

the cervix

Question 13

What is the difference between initiator, promotor and complete carcinogens?

Answer 13

Initiators are genotoxic i.e. can chemical modify or damage DNA
Promotors are non genetic and induce proliferation and DNA replication
Complete carcinogens can do both

Question 14

name a complete carcinogen?

Answer 14

UV light

Question 15

What 2 things does mutation indiction (initiation) require?

Answer 15

Chemical modification of DNA
Replication of modified DNA and mis-incorporation by DNA polymerase - requires 2 rounds of replication for a mutations to be fixed

Question 16

The presence of what in the DNA exacerbates the tendency of polymerase to make mistakes?

Answer 16

Chemical modifications - miscoding or non-coding adducts or lesions

Question 17

In which 2 ways do promotor carcinogens contribute to carcinogenesis?

Answer 17

1) They can stimulate the 2 rounds of DNA replication required for mutation fixation
2) Secondly they can stimulate clonal expansion of mutated cells, which enables the accumulation of further mutations

Question 18

Why is clonal expansion of a cell with 1 mutation so important in carcinogenesis

Answer 18

To form a malignant cell need 2-8 specific mutations, very hard for a cell to acquire these without significant clonal expansion

Question 19

Give 2 examples of endogenous mutagen

Answer 19

1) Oxygen radicals

2) Lipid metabolism byproducts

Question 20

Describe the process of initiation, promotion and progression using a mouse model skin tumour?

Answer 20

1) Genotoxic initiating agent damages DNA
2) Promoting agent fixes the damage as a mutation and converts normal calls into mutant initiated cell
3) Promoting agent stimulates clonal expansion of initiated cells to produce papillomas
4) Further rounds of mutations and clonal expansion allows papilloma to progress to carcinoma

Question 21

What is meant by a TSG?

Answer 21

tumour suppressor gene