CANCER- DNA damage and repair

Question 1

what can damage DNA?

Answer 1

Chemicals (carcinogens)	– these	may	come	from…
o Diet	(additives	+	preservatives,	for	example	nitrates)
o Lifestyle	(smoking,	alcohol)
o Environment	(pesticides,	although	not	that	important)
o Occupation	(mine	workers,	tarmack	layers)
o Medicine	(chemotherapy)
o Endogenous	substances	(eg	viruses)

radiation
o Ionizing (eg isotope tracers, X-rays)
o Solar (UV radiation)
o Cosmic (the earth is protected from high energy radiation including cosmic
radiation, but for example in airplane flights exposure increases)

Question 2

what is a common modification of DNA base?

Answer 2

oxidation of thymine to form thymine glycol

Question 3

what is photodamage?

Answer 3

Ultraviolet light is absorbed by the nucleic acid bases, and the resulting influx of energy can induce chemical changes and form dimers

Question 4

what are the consequences of DNA damage?

Answer 4

DNA damage leads to mutation which can lead to cancer

damaging DNA is an important strategy in cancer therapy to stop the cells from proliferating

Question 5

what are polycyclic aromatic hydrocarbons?

Answer 5

Common environmental pollutants
Formed from combustion of fossil fuels
Formed from combustion of tobacco

Question 6

what are the stages of mammalian metabolism?

Answer 6

phase 1:
addition of functional groups
mainly cytochrome p450 mediated

phase 2:
conjugation of Phase I functional groups to generate a polar (water soluble) metabolite

Question 7

what is a potent bladder carcinogen?

Answer 7

2-naphthylamine

at first it is not a carcinogen then it is metabolised and the acidic pH of the urine polarises the metabolite producing a that is a highly DNA-reactive electrophile and it causes bladder cancer

Question 8

what are the different types of DNA repair?

Answer 8

direct reversal of DNA damage

base excision repair

nucleotide excision repair

during or post- replication repair

Question 9

describe direct reversal repair mechanism

Answer 9

involves the reversal or simple removal of the damage by the use of proteins which carry out specific enzymatic reactions

photolyases repaire thymine dimers (not UV light)

O6 methylguanine-DNA methyltransferase (MGMT) directly reverses some simple alkylation adducts.
- remove bases which have undergone methylation because the recognise specific bases with specific recognition sites on them

Question 10

describe base excision repair

Answer 10

remove base part of a nucleotide and the rest of the strand stays intact
via DNA glycosylase

the backbone is broken by AP-endonuclease

then the base is inserted into the strand by DNA polymerase

DNA ligase repairs the backbone

Question 11

describe nucleotide excision repair

Answer 11

here a stretch of DNA is removed, therefore the chain does not remain in tact

1. endonuclease breaks backbone
2. helicase removes a chain of bases
3. DNA polymerase inserts bases
4. DNA ligase fixes backbone

Question 12

what are the different methods for testing for DNA damage?

Answer 12

ames test

Chromosomal aberrations

In vitro micronucleus assay

Bone marrow micronucleus assays