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Oncology > Chapter 2 > Flashcards

Chapter 2 Flashcards

1
Q

Which (epi)genetic alterations can lead to cancer?

A
  1. Stability genes inactivation (used for DNA repair)
  2. Oncogenes activation ( example: Growth factors)
  3. Tumor suppressor genes inactivation
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2
Q

Give examples of small changes in DNA

A
  1. Base pair substitution
  2. Deletions or insertions
  3. Single and Double strand breaks
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3
Q

Give examples of large changes in DNA

A
  1. Change in DNA content per nucleus
  2. Chromosome rearrangements
  3. Gene amplification
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4
Q

Why are strand breaks extremely dangerous?

A

They increase the risk of large deletions and major chromosome rearrangements

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5
Q

What are some exogenous causes of DNA damage?

A
  1. Smoking
  2. Drinking
  3. UV light
  4. Other forms of radiation
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6
Q

What are some endogenous causes of DNA damage?

A
  1. Mistakes in replication

2. Reactive oxygen species

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7
Q

Give some examples of DNA damage that could happen and their possible cause

A
  1. Pyrimidine dimer (UV light)
  2. Strand breaks (X-rays)
  3. Bulky adducts (PAH)
  4. Base loss (Spontaneous hydrolysis)
  5. Nitrogen crosslinks (cisplatin, MMC, nitrogen mustard)
  6. Intrastrand adducts (cisplatin)
  7. Modified bases (Alkylating agents, ROS)
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8
Q

How is 8-oxoguanine formed?

A

Through ionizing radiation or cellular aging

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9
Q

Why is 8-oxoguanine mutageninc?

A

DNA polymerase reads it as a thymine, and it will transcribe a thymine instead of guanine on the next strand

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10
Q

Give some examples of DNA repair mechanisms and when they are applied

A
  1. Base excision repair - When one base is damaged
  2. Nucleotide excision repair - When there are bulky adducts
  3. Mismatch repair - for replicaion errors
  4. Recombination repair - strand breaks
  5. complex repair - Cross-links
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11
Q

What are some recessive cancer-predisposition syndromes?

A
  1. Ataxia telangiectasia (defect in the ATM kinase)
  2. Fanconi anemia
  3. Xeroderma pigmentosum
  4. Nijmegen breakage syndrome
  5. Bloom’s syndrome
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12
Q

What are some dominant cancer predisposition syndromes?

A
  1. HNPCC (colon cancer)

2. BRCA1/BRCA2 (breast cancer, ovary cancer and pancreas)

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13
Q

What protein is important for the repair of double strand breaks?

A

Ataxia enzyme (ATM)

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14
Q

What are the steps in repairing a strand break?

A

The strand breaks. ATM gets activated. Exonuclease complex (RAD50/MRE11/NBS1) digest damaged strands. Digested strand binds to a homologous combination on an intact strand, then it’s being restored.

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15
Q

What are ATM, FA and BRCA proteins important for?

A

DNA repair and sensing of DNA damage.

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16
Q

Why are people with dysfunctional ATM, FA and BRCA at higher risk of developing cancer if they smoke and drink?

A

Because their body is less effective at repairing DNA damage

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17
Q

What is base excision repair and what is it used for?

A

BER is used to correct a base (pyrimidine/purine) that has been damaged. Only the base is removed

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18
Q

What is the role of DNA glycosylase?

A

It senses a damaged DNA base and removes it, leaving an abasic site

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19
Q

Which enzyme replaces the missing base in BER?

A

DNA polymerase beta

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20
Q

What is the role of MUTYH?

A

It is a DNA glycosylase that is involved in the repair od 8-oxoguanine

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21
Q

What is Nucleotide excision repair?

A

A stretch of nucleotides is removed and replaced. Usually the stretch is 25 ~ 30 base pairs long

22
Q

What kind of damage induce NER?

A

UV-induced pyrimidine dimers and large chemical adducts

23
Q

what disease is related to mistakes during NER?

A

Xeroderma Pigmentosum

24
Q

What disease is related to mistakes in BER?

A

Familial adenomatous polyposis

25
Q

Which proteins are involved in mismatch DNA repair?

A

MSH2 and MLH1

26
Q

What cancer is related to dysfunctional MSH2 and MLH1?

A

HNPCC

Hereditary Non-Polyposis Colorectal Cancer

27
Q

what is ionization radiation?

A

Radiation that can cause an atom to lose an electron

28
Q

How can free electrons damage the DNA?

A

Through binding to other atoms in the DNA or by creating ROS

29
Q

What is the most dangerous ROS?

A

Hydroxyl radical OH

30
Q

what is the unit “Gray” ?

A

Gray is the absorbed dose in tissues

1 Gy = deposit of 1 joule/ kg tissue

31
Q

What is the unit “Sievert”?

A

Sievert is used as an unit for biological damage

Sv = (dose in Gy) x radiation quality factor

32
Q

Give some examples of Particle Radiation

A
  • alpha (2p + 2n)
  • deuteron (p + n)
  • beta (electron)
  • neutron
  • proton
  • heavy particles (carbon ions)
33
Q

Give some examples of EM radiation

A
  • Photons
  • X-rays
  • Gamma rays
34
Q

What is Linear Energy Transfer?

A

The average energy per distance that a charged particle deposits in a tissue (keV/um)

35
Q

The higher the LET…

A

… the more cells are getting killed per Gy

36
Q

What is the latent period of cancer?

A

The mean time between exposure to radiation and the manifestation of a tumors

37
Q

what is the Latency for leukemia after being exposed to radiation?

A

Around 10 ~ 15 years

38
Q

what is the most frequent cancer induced by radiation?

A

Leukemia

39
Q

Which age group is the most sensitive to radiation?

A

Children

40
Q

What is an example of non-ionizing radiation?

A

UV radiation. It does not cause ionization, but it causes pyrimidine dimers and point-mutations

41
Q

What is a genotoxic compound?

A

A compound that can induce DNA damage

42
Q

How can non-genotoxic compounds promote cancer?

A

By stimulating cell proliferation

43
Q

what are the most important DNA-damage inducing carcinogens?

A
  1. PAH
  2. Aromatic amines
  3. Nitrosamines
  4. Alkylating drugs
44
Q

Where can you find nitrosamines?

A

In Tabacco smoke

45
Q

Give some examples of anti-oxidants

A

Gluthatione

Vit A, C and E

46
Q

What are some examples of alkylating agents?

A
  1. Chlorambucil
  2. Temozolomide
  3. Cyclophosphamide (has to be metabolized)
47
Q

What are some platinum-based drugs?

A

Cisplatin and carboplatin

48
Q

What are some antimetabolites?

A

Methotrexate

5-FU

49
Q

what are some organic drugs?

A

Doxorubicin (topoisomerase II inhib)

Vincristine (microtubuli inactivator)

50
Q

What are some examples of intrinsic drug resistance by cancer cells?

A
  1. Location in the body (distance from blood vessels) - Hypoxic cells are more resistant to radiation
  2. Heterogeneity - cells have different resistances to radiation and drugs
  3. Drug resistance can be acquired

Oncology (8 decks)

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