Environmental Basis of Cancer

Question 1

What is a complete carcinogen?

Answer 1

Something sufficient to cause cancer

Question 2

How do initiators and promoters cause cancer?

Answer 2

Initiator: PAHs, Promotor: phorbol ester
Following an iniator, must be followed by multiple doses of successive promoters, at any time period.
The iniator affect is irreversible (mutation)(Sequence) vs promoter being reversible(signalling change)(gene expression)

Question 3

What summarises UVA vs UVB?

Answer 3

All UVA vs UVB respectively
Wavelength: 320-400; 290-320
Sunburn: weak; strong
Target: ROS; DNA
Carcinogen: weak potent promoter; complete carcinogen

Question 4

What gene is often affected and how?

Answer 4

TSG gene p53. Often C to T/ CC to TT changes

dipyridine affected form cyclobutane dimers

Question 5

What happens with subsequent exposures?

Answer 5

p53++ peeling
p53+- reduced apoptosis, expanding mutant clones
p53– loss of apoptosis, malignant change

Question 6

What can be said about lung cancers?

Answer 6

Tobacco has 60 known carcinogens

Contains PAHs and NNK

Question 7

How do PAHs and NNKs affect lung cell?

Answer 7

PAHs (eg BalphaP): G to T change, affecting AchR
NNK: Methylates Guanine, causing a G to A switch. (G-C; mG-C; G-T; A-T

affects nACHRs and Beta ARs, promoting proliferation and addictive part of brain

Question 8

How does Hep B cause liver cancer as a promoter

Answer 8

on the p53 gene at codon 249. The AGG is binded to by AFB-1 (on the final G). As a result, changes to AGT.

Hep B produces X protein, which inhibits apoptosis (due to AFB-1 binding), and repair. It also causes cell death and regeneration leading to proliferation. ALso activates ras (oncogene)