Cancer

Question 1

What evidence is required to establish the link between oxidative stress and cancer?

Answer 1

Incidence increase with age

Environmental agents inducing OS should enhance susceptibility.

Early onset cancers associated with repair defects in antioxidant defences.

Question 2

What have mouse models shown regarding HBV and hepatocellular carcinoma?

Answer 2

sustained accumulation of 8-oxo-dG atrats earlu and increases with disease –> HCC.
8-oxo-dG can –> missense mutations in cancer related genes.

Question 3

How are free radicals implicated in tumourigenesis?

Answer 3

Pro-inflammatory cytokines induce iNOS and COX2 which produce free radicals.
COX2 and iNOS are transcriptionally repressed by p53.
Insufficient repair of DNA damage –> procarcinogenic response –> cancer cells.
OR activate cell stress response to repair or kill cells.
Outcome dependent on [], genetics and microenvironment.

Question 4

How does NO modify p53?

Answer 4

WT p53 transrepresses iNOS.

Expose cells to high levels of NO during chronic inflammation and mutant p53 –> increase cancer susceptibility.

Question 5

What p53 mutations are associated with NO?

Answer 5

Increased p53 mutations at codons 247, 248 + high iNOS expression in inflamed UC colon areas.
High iNOS + GC to TA transversions at codon 249 of p53 in haemochromatosis.

Question 6

Which genetic polymorphisms are linked to FRs?

Answer 6

OGG1 - oesophagus, lung, prostate
BRCA2 - breast
MnSOD - Breast
GPx - lung.