Cancer And DNA Flashcards

1
Q

Name a few characteristics of cancer cells

A

Grow in the absence of growth signals
Ignore apoptosis signals
Spread to other areas of the body
Accumulate changes in their chromosomes

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2
Q

Why is cancer so difficult to cure

A

Every tumour is unique - single tumour contains diff populations of cells
Treatment leads to evolution of drug resistant tumour cells

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3
Q

What are the current aims and strategies of cancer drug discover

A

Identify underlying molecular pathologies
Target the identified differences between normal and tumour cells

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4
Q

Describe Knudson’s Two Hit hypothesis

A

In order for a cell to become cancerous both of the cells tumour suppressor genes must be mutated

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5
Q

Describe cancer

A

Family of genetic disease caused by germline and somatic mutations and chromosomal aberrations

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6
Q

What causes cancer

A

The accumulation of mutations in genome arsing from DNA damage

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7
Q

What genes are mutated in cancer

A

Oncogenes (+tive regulators of cell growth)
Tumour suppressor genes (-tive regulators of cell growth)
Apologise and lifespan-regulating genes
Mutator genes (DNA damage surveillance and repair)

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8
Q

Name a few environmental factors that can lead to cancer

A

Sex -> HPV -> Cervical
Alcohol -> Cirrhosis -> Liver
Stress -> Inflammation -> Various
Viruses -> EBV -> Burkitt’s lymphoma

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9
Q

Name examples of environmental carcinogens

A

X -irradiation -> radiotherapy -> breast
UV irradiation -> sun -> skin
Anti cancer drugs -> chemotherapy -> leukaemia
Benzopyrenes -> tobacco -> lung

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10
Q

What influences ‘the cancer lottery’

A

Casual mechanism in loving evolutionary mismatches and intrinsic fallibility
= mutations that enable increased cell survival
-> Darwinian selection will then select for these ‘positive attributes’

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11
Q

Describe the mechanism of DNA damage by carcinogens

A

Metabolised in body -> electrophiles that react w nucleic acid
E.g benzo[a]pyrene -> BPDE -> covalent adduct + guanine

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12
Q

Describe the mechanism of DNA damage by ionising radiation

A

X-rays cause oxidative damage to DNA
OH radicals damage nucleic acids
Result of hydrolysis of water by ionising radiation

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13
Q

Describe the mechanism of DNA damage by UV radiation

A

UVA: produces mainly reactive O2 species (ROS)
UVB: produces thymine photoproducts in the DNA

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14
Q

Describe the absorptions of the 3 types of UV

A

UVA 320-400nm - 95% reaching earth surface
UVB 280-320nm - Most absorbed by ozone layer
UVC <290nm - absorbed by O2

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15
Q

Describe the mechanism of DNA damage by sun damage

A

UV damages some cells -> can’t be repaired and are destroyed as risk of becoming cancerous
Some damage may remain, increasing cancer risk

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16
Q

What are the 3 types of UV

A

UVA: penetrates deep into skin, causes ageing
UVB: responsible for sunburns and can cause cancer
UVC: most dangerous of all, blocked by ozone

17
Q

Describe the mechanism of DNA damage by chronic infections

A

Chronic infections lead to persistent inflammation at sites of infection = damage to cells

18
Q

Describe the mechanism of DNA damage by endogenous causes

A

Hydrolysis of glycosyl bonds = base loss in DNA
Exposure to free radicals and oxidation
Methylation of bases in DNA via SAM
Replicating errors by DNA polymerase = deletions
Spontaneous decay of DNA

19
Q

What is one of the most server side effects of cancer therapies

A

Diagnosis of second primary cancers unrelated to original ancerts

20
Q

Describe the mechanism of DNA damage by DNA replication

A

Template lacks necessary information to form correct sentence =
Insertion of wrong base
Addition/deletion of short sequences
Double strand breaks

21
Q

What are the consequences of incorrect DNA replication

A

Loss of chromosome segments
Exchange of sequence (recombination)
Stalling of replication fork @ damaged sites

22
Q

What are the 2 most frequently mutated genes in smoking related lung cancer

A

K-ras (oncogenes) and p53 (tumour suppressor)
Benzo[a]pyrene linked to these mutations

23
Q

How does benzo[a]pyrene cause a mutation

A

It’s epoxide binds to guanine in nucleus
If unrepaired G-C -> T-A (trans version mutation)

24
Q

How does the K-ras oncogene

A
25
Q

How does a mutation on p53 cause its inactivation

A

Undergo G->T transversion in 3 key sites

26
Q

What are the consequences of base substitutions

A

No change
Loss/change in activtiy of gene product
Change of amino acid

27
Q

What are the consequences of deletions and insertions

A

Loss of function of gene product

28
Q

What are the consequences of gene amplification

A

Repeated firing of replication of origins
Over-expression of gene product

29
Q

What are the consequences of chromosomal rearrangements

A

Loss of gene(s)
Alterations in expression
Changes in function
Creation of new fusion genes

30
Q

What cell types are susceptible of DNA damage

A

Cells w high proliferation capacity e.g intestinal epithelium
Cells exposed to environmental carcinogens e.g skin and lungs

31
Q

What is the spontaneous mutation rate vs DNA damage

A

10-6 -> 10-8 per cell doubling per gene
DNA damage can increase rates by 10->100 fold

32
Q

What are the genome defence strategies

A

1- Range of interactive DNA damage repair pathways
2- DNA damage activated enzymes
3- Detoxifying enzymes e.g free radical scavengers
4- Apoptosis (in multi-cellular organisms)

33
Q

What are emerging hallmarks of cancer

A

Capability to modify or reprogram cellular metabolism
Evading immunological destruction

34
Q

What are the enabling characteristics of cancer

A

Genomic instability -> mutation gives cells genetic alterations = tumour progression
Inflammatory response but innate immune cells -> tumour promoting