OS and Skin

Question 1

Give examples of endogenous chromophores.

Answer 1

Aromatic AAs, melanin and precursors, porphyrins, flavins, DNA.

Question 2

Are ROS always ‘bad’?

Answer 2

They are involved in; cell signalling and gene transcription (UVA-induced ROS induces transcription e.g. HO-1 in vitro).

Question 3

Give an example of a comet assay.

Answer 3

Effect of pre-UVR incubation with VE on CPD and 8-oxoGus.
Mean % of tail DNA HaCaTs exposed to UVA doses of 5 and 10 J/cm2.
VE reduces lesions.
Increasing dose increases lesions.
Difficult in vivo but good in vitro.

Question 4

What type of repair process is required after UVR damage?

Answer 4

NER (unscheduled DNA synthesis repair involving ~30 proteins).

Question 5

Why is UV particularly damaging?

Answer 5

Shindo et al (1994) - UVR on mouse skin - decreases antioxidants! (damage to tissue and decrease in anti’).

Question 6

How does a comet assay work?

Answer 6

DNA damage analysis conducted with single cell gel electrophoresis in combination with DNA repair enzymes.
E..g. T4N5 recognises CPD,, chops DNA, then pulled by an electric current.

Question 7

What did Agar et al (2004) show regarding p53 mutations?

Answer 7

In SCC in basal layer - UVA accounted for greater %.

In epidermis UVB more responsible.

Question 8

Which lesions are more important in skin cancer and how do we know this?

Answer 8

CPDs.
Jans et al (2005).
Transgenic mice with photolyase genes. Those with CPD photolyases less susceptible to skin cancer than those with only 6,4PP lyases.