1 - Roles of DNA damage and repair in carcinogenesis

Question 1

Can cancer be solid or liquid

Answer 1

Both

Question 2

Why can cancer be difficult to cure

Answer 2

Tumours are heterogenous (unique)
Treatment leads to resistant cells

Question 3

Why does cancer risk increase with age

Answer 3

Increased exposure so smoking, alcohol, burnt food, sunlight exposure

Question 4

What is Knudson’s two hit hypothesis

Answer 4

Both chromosomes of the gene (tumour suppressor genes) have to be damaged to form a tumour. Can happen quicker if there is already one inherited damaged chromosome

Question 5

4 genes mutated in cancer

Answer 5

Oncogenes
Tumour suppressor genes
Apoptosis genes
Mutator (caretaker) genes

Question 6

How can ionising radiation cause cancer

Answer 6

X rays cause oxidative damage
OH radicals from hydrolysis if water damage nucleic acids

Question 7

How can UV cause cancer

Answer 7

UVA –> produces ROS
UVB –> produces thymine photoproducts

Question 8

How can carcinogens cause cancer

Answer 8

Cigarette smoke - convert benzo[a]pyrene to BPDE which forms a covalent adduct with guanine

Plant fungi - anflatoxin is oxidised in the liver and covalently binds to guanine

Question 9

How can chronic infection cause cancer

Answer 9

Gastric tumours form heliobacter pylori

Bladder cancer from schistosoma / parasitic worms

Cervical cancer from HPV

Question 10

What forms of spontaneous damage can occur to cause cancer

Answer 10

Hydrolysis of glycosyl bonds - base loss

Oxidation from OH. production during aerobic metabolism

S-adenosyl methionine (SAM) can methylate bases

DNA polymerase acting as replication forks can cause replication errors

Question 11

How can cancer therapy cause cancer

Answer 11

They are DNA damaging to attack tumour but can also attack normal DNA
- Cyclophosphamide

Question 12

When do DNA replication errors occur

Answer 12

In S phase

Question 13

What errors occur during DNA replication

Answer 13

Putting the wrong base in
Addition or deletion of short sequences
Double strand breaks

Question 14

Consequences of DNA replication errors

Answer 14

Loss of chromosome segments
Exchange of sequence (could be 2 DSBs and the wrong pairs put back together)
Stalling of replication fork (get stuck at damaged site and cells gets stressed and replication machinery get backed up)

Question 15

What are the cells most susceptible to become cancerous

Answer 15

Highly proliferative cells (haematopoietic stem cells, intestinal epithelium)

Cells exposed to environmental carcinogens (skin, lung, gut)