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Momna Mcq > DNA damage > Flashcards

DNA damage Flashcards

1
Q

What are the two classifications of DNA damage?

A

Spontaneous

Environmental

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2
Q

What is DNA damage?

A

Modifications in the molecular structure of the genetic material

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3
Q

Spontaneous DNA damage is a result of what?

A

Normal metabolism

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4
Q

Environmental DNA damage is a result of what?

A

Environmental factors (mutagens and carcinogens) found in food, water etc

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5
Q

What is a carcinogen?

A

Induces unregulated growth

Epithelium in origin

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6
Q

What is a mutagen ?

A

Induces change in genetic material

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7
Q

What are the 4 classes of spontaneous DNA damage?

A

Tautomeric shifts
Deamination
Depurination/depyramidination
Oxidative damage

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8
Q

What is a tautomeric shift?

A

When any of the 4 bases undergo spontaneous rearrangement in bonding to form a tautomer

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9
Q

The tautomer of amino is ?

A

Imino

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10
Q

What 2 bases form imino forms of tautomers usually?

A

Cytosine and adenine

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11
Q

What is the tautomeric form of a Keto called?

A

Enol

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12
Q

What bases form Enol tautomer?

A

Thymine and guanine

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13
Q

What is deamination?

A

When the entire amine (nh2) group is removed

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14
Q

What reaction is deamination?

A

Hydrolytic

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15
Q

What factors are deamination dependent upon?

A

Temperature and ph

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16
Q 
List the deaminated forms of the following bases.... 
cytosine 
Adenine 
Guanine 
5-methyl cytosine
A

Uracil
Hypoxanthine
Xanthine
Thymine

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17
Q

What is depurination/depyrimidination?

A

When the entire base is lost

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18
Q

Under what conditions do depurination / depyrimidination thrive?

A

Acidic ph

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19
Q

What reaction occurs during depurination/ depyrimidination

A

Hydrolysis of the N - glycosidic bond via protonation of water

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20
Q

What reaction aids depurination/ depyrimidination?

A

Protonation of water

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21
Q

What is produced during depurination/ depyrimidination?

A

A basic sites

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22
Q

Are purines or pyrimidines lost faster and by what factor?

A

Purines

20x faster

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23
Q

What base is depurinated faster under ACIDIC conditions?

A

Guanine 1.5 times faster

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24
Q

Oxidative damage is a result of what?

A

Normal aerobic metabolism

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25
Q

What does oxidative damage form ?

A

Reactive oxygen species (ROS)

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26
Q

Give 4 examples of ROS

A

Singlet oxygen
Organic peroxides (hydrogen peroxide)
Superoxide anion radicals
Fenton reaction generated hydroxyl radicals

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27
Q

What is the most frequent type of DNA damage?

A

Oxidative damage

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28
Q

Why is oxidative damage the most common type of DNA damage?

A

Continuous cellular production of ROS

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29
Q

What is the downstream effect of ROS?

A

Convert target molecules into radicals when trying to get a full configuration of electrons and so generate chain reaction until 2 radicals pair

30
Q

In addition to normal metabolism, under what other mechanisms are ROS generated?

A

Long wavelength IV

IR

31
Q

What mechanism has cells developed in order to protect against ROS ?

A

Scavengers

32
Q

What are the two classifications of environmental DNA damage ?

A

Physical agents

Chemical agents

33
Q

List the physical agents that cause environmental DNA damage..

A 
UV
Ionising radiation (IR)
34
Q

What are the two main UV light induces DNA photo products?

A

Cyclobutane pyrimidine dimers

Pyrimidine 6-4 pyrimidone photo products

35
Q

What are CPDs

A

Bond formation between adjacent pyrimidine on the SAME DNA strand due to influx of energy when bases absorb uv light

36
Q

What is the order of frequency of CPDs?

A

T-T> T-C/C-T > C-C

37
Q

What does a CPD cause ?

A

A kink in the DNA strand when the two pyrimidines are pulled in closer than normal

38
Q

What bond is formed when cpd are formed?

A

DOUBLE covalent bond

39
Q

What are 6-4 PPs

A

pyrimidine dimer when a SINGLE covalent bond is formed between the 6 position of one pyrimidine and the 4 position of the adjacent pyrimidine on the 3’ side

40
Q

What is the order of frequency of the pyrimidine dimer formation

A

T-C > C-C > T-T > C-T

41
Q

What type of pyrimidine dimer he the greatest distortion? List the values?

A

44 degree bend vs 7-9 degree bend (64PP vs CPD)

42
Q

What is unique about IR damage?

A

Causes damage to all cellular components not only DNA

43
Q

What is the majority of IR damage due to? Give a value

A

80% - production of ROS due to water radiolysis

44
Q

80% of IR damage is due to the production of ROS, via what mechanism are these ROS formed ?

A

Radiolysis of water

45
Q

65% of IR Damage is due to what?

A

Hydroxyl radical

46
Q

IR had the same consequence as oxidative damage … what is this consequence?

A

Base dimerisation

DNA protein crosslinks

47
Q

Why is IR damage so severe ?

A

Capable of depositing numerous ROS in the same DNA locale and therefore producing multiple closely spaced damages on BOTH strands of DNA

48
Q

Multiple damaged sites are formed during IR damage, what does this lead to ?

A

Ds DNA breaks

Clustered base damage

49
Q

What beneficial aspects do chemical agents, that also cause DNA damage, possess?

A

Chemotherapeutics

50
Q

What do alkylating agents do?

A

Add alkyl groups to electronegative groups

51
Q

What are alkylating agents structure like?

A

Electrophilic

High affinity for nucleophilic centres

52
Q

What are the two classes of alkylating agents?

A

Mono functional and bifunctional (single/2 reactive groups that react with single site/2 sites on DNA)

53
Q

How to alkylating agents act as chemotherapeutics?

A

Cross link guanine bases in DNA double helix and so strands can’t recoil a process necessary for replication and so division

54
Q

What is a second mechanism by which alkylating agents cause DNA damage?

A

Cross linking agents - form cross bridges (bonds between atoms) in DNA

55
Q

Cross bridges are formed by what type of alkylating agent?

A

Bifunctional - 2 DNA binding sites

56
Q

How does cross linking agents acts as chemotherapeutics ?

A

Cross linking prevents strand separation and so prevents synthesis and transcription

57
Q

Cross linking agents are used in what 2 chemotherapeutic drugs?

A

Carboplatin

Cisplatin

58
Q

What are psoralens?

A

Photosensitising furocaumarins that upon photoreactivation with long wavelength UV form covalent adducts to pyrimidine bases on DNA

59
Q

What is the result of psoralens?

A

DNA crosslinks
Distortion
Unwinding of DNA

60
Q

Psoralens can cause what?

A

Phytophotodermititis (found in fruit and veg)

61
Q

What is the conformation of psoralens?

A

Planar tricyclics configuration

62
Q

How does the structure of psoralens aid their function?

A

Planar tricyclic allows it to slip between base pairs on DNA

63
Q

How do electrophilic reactant metabolites become reactive ?

A

Undergo metabolic conversion in the liver by e.g cytochrome p-450 system

64
Q

How is the electrophilic metabolite AAF carcinogenic?

A

Reacts with c8 and n2 positions of nuclei acids to form DNA adducts

65
Q

What does AAF stand for?

A

N-2-acetyl-2-amino fluorescence

66
Q

What is benzo [a] Pyrene ?

A

Polycyclic aromatic hydrocarbon

67
Q

What is the most carcinogenic compound?

A

Benzo[a] Pyrene

68
Q

How are benzo[a] Pyrenes toxic ?

A

Metabolised by liver enzymes to excretable products and potent epoxides that covalently bind to amino group of guanine

69
Q

Aflatoxinsare an example of what

A

Mycotoxin

70
Q

What is the most reactive form of aflatoxin?

A

B1

71
Q

What is the action of B1 aflatoxin

A

Epixide form (after metabolism in the liver) attacks bases (especially guanine) to form DNA adducts

Momna Mcq (4 decks)

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