Environmental Basis of Cancer

Question 1

What is a complete carcinogen?

Answer 1

A substance that is sufficient to cause cancer

Question 2

What is the only way that initiators and promotors combine to cause a tumour?

Answer 2

The initiator comes first and the promotors are delivered in rapid succession

Question 3

Describe the PAH initiator in terms of its duration, target, effects and role in carcinogenesis?

Answer 3

Permanent, targets DNA, causes mutations, alters gene sequence and delivers potentially carcinogenic damage

Question 4

Describe the phorbol promoter in terms of its duration, target, effects and role in carcinogenesis?

Answer 4

Transient, targets proteins (enzymes), affects signalling pathway, modulates gene expression, stimulates outgrowth of initiated cells

Question 5

What type of carcinogen is UV?

Answer 5

Complete

Question 6

Describe UVB

Answer 6

290-320
weak penetrance
causes sunburn
damages DNA
complete carcinogen

Question 7

Describe UVA

Answer 7

320-400
strong penetrance
does not cause sunburn (mostly)
generates reactive oxygen species
promoter and complete carcinogen

Question 8

Describe the process from CC-GG to TT-AA mutation in p53 gene after UV exposure

Answer 8

CC-GG absorbs UV and forms cyclobutane dimer
Replication by DNA polymerase η puts AA connected to the dimer. This adds heterozygous mutant p53 genes to the gene pool. Excessive heterozygous mutant p53 leads to homozygous mutant p53 in the gene pool.
The dimer is “repaired” and TT-AA is formed

Question 9

What are the different capacities of the p53 gene varieties?

Answer 9

Homozygous wild type=affective apoptosis
Heterozygous mutant=reduced p53 mediated apoptosis and expanding mutant clones with each sunburn
Homozygous mutant=loss of apoptosis and malignant change

Question 10

What are the two key tobacco carcinogens, what do they do and what is their signalling activity?

Answer 10

PAH G to T mutations binds aryl hydrocarbon receptor (AhR)
Nicotine Derivative (NNK) G to A mutations binds β-AR and nAChR

Question 11

Which parts of the body have NNK receptors on them besides the lungs?

Answer 11

CNS
Endothelial cells
Adrenal medulla

Question 12

What is the process from G-C to A-T with NNK?

Answer 12

G-C to O^6MegG-C to O^6MeG-T to A-T

Question 13

What does NNK promote in the lungs?

Answer 13

Proliferation, survival and invasion

Question 14

How do aflatoxin and hepatitis B work together to produce hepatocellular carcinoma?

Answer 14

Aflatoxin=initiator
HBV=promoter
G-C exposed to AFB1
G-C attached to AFB (p53 apoptosis can occur here)
G-A attached to AFB
T-A
Carcinoma
Simultaneously HBV is causing cell death, inflammation, regeneration and proliferation. Also producing an X protein that inhibits p53 and repair (from G-C attached to AFB back to G-C) and stimulating Ras protein

Question 15

What is the Ras protein?

Answer 15

An oncogene