tumour pathology 4 Flashcards

1
Q

what is a cell cycle?

A

the interval between mitotic divisions

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2
Q

what are the phases of the cell cycle, and what happens in each?

A
  1. G1 - synthesis of components required for DNA synthesis
  2. S - DNA synthesis
  3. G2 -preparation for mitosis
  4. M - mitosis and cell division

G0- extension of G1, quiescent state, dormant

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3
Q

when does DNA repair occur?

A

G2 phase

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4
Q

when can the cell cycle be affected by external factors?

A

in the G1 phase

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5
Q

examples of external factors

A

hormones, cytokines, growth factors, stroma

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6
Q

where are the checkpoints of the cell cycle?

A
  • G1 checkpoint at the G1/S transition
  • G2 checkpoint at -the G2/M transition
  • M checkpoint between metaphase and anaphase
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7
Q

where is the cell cycle arrested if cell size is inadequate?

A

G1 or G2

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8
Q

where is the cell cycle arrested if nutrient supply is inadequate?

A

G1

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9
Q

where is the cell cycle arrested if essential external stimuli are lacking?

A

G1

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10
Q

where is the cell cycle arrested if DNA is not replicated?

A

S

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11
Q

where is the cell cycle arrested if DNA is damaged?

A

G1 or G2

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12
Q

where is the cell cycle arrested if chromosomes mis-align

A

M-phase

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13
Q

how do checkpoints work?

A
  1. cyclin dependent kinases are present in the cell
  2. cyclin levels rise if the checkpoint has the go-ahead.
  3. these bind to CDKs, activating them.
  4. the active CDKs then act by phosphorylating sybstrates
  5. these phosphorylated substrates are required for the next stage of the cell cycle

the cell cycle is also regulated using CDK inhibitors

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14
Q

what does INK4A inhibit?

A

CDK4

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15
Q

INK4A inhibitors

A

p16^INK4A
p15^INK4B
p18^INK4C
p19^INK4D

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16
Q

CIP/KIP inhibitors

A

p21^CIP1

17
Q

what does the retinoblastoma gene encode for?

A

pRb

18
Q

when is pRb active?

A

when it is hypophosphorylated

19
Q

when is pRb inactive?

A

when it has been phosphorylated by cyclin D/CDK complexes

20
Q

what is the function of pRb?

A

E2F transcription factor, this activates vital target genes for the stimulation of cell cycle entry

21
Q

how do oxidising and alkylating agents cause carcinogenesis?

A

they critically damage purine and pyrimidine bases in DNA

22
Q

what is a DNA adduct?

A

covalently bound products of DNA and a chemical carcinogen

23
Q

how does radiation damage DNA?

A

damages the purine and pyrimidine bases

24
Q

types of ionising radiation

A
  • UV (UV-B in sunlight)
  • X-rays
  • Gamma radiation
25
Q

what are the two regulatory pathways regularly disrupted to cause cancer?

A
  1. The cyclin D-pRb-E2F pathway

2. p53 pathway

26
Q

which checkpoint is usually dysregulated in cancer cells and which four genes are mutated?

A

G1/S checkpoint

Rb, CDK4, cyclin D and p16

27
Q

p53 function

A

maintains genomic integrity.

does this by inducing cell cycle arrest at G1 or facilitating DNA repair or inducing apoptosis if DNA damage is severe