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Neoplasia Carcinogenesis Flashcards

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1
Q

What are the 4 steps involved in carcinogenesis?

A
  1. Independence from normal control mechanisms
  2. Avoid apoptosis
  3. Immortality
  4. Metastatic capability
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2
Q

What phase is G1 known as in the cell cycle?

A

Resting phase

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3
Q

What phase is G2 known as in the cell cycle?

A

Gap phase

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4
Q

What occurs during S phase of the cell cycle?

A

DNA replication

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5
Q

What occurs during the M phase of the cell cycle?

A

Mitosis

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6
Q

What is a proto-oncogene?

A

Potential oncogene - normal genes that regulate cell growth and differentiation.

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7
Q

What is an oncogene?

A

Activated proto-oncogene - causes cell proliferation and does not recognise growth inhibitory signals = tumor formation.

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8
Q

What is the initiator in the ‘initiator/promoter’ theory?

A

A carcinogen that causes irreversible DNA change that does NOT induce full blown neoplasia in a cell

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9
Q

What is the promoter in the ‘initiator/promoter’ theory?

A

Increase the proliferation of neoplastic cells

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10
Q

Induced neoplasms take a long time due to a multi_____ process and ________ exposure to the agent

A

Induced neoplasms take a long time due to a multi-step process and prolonged exposure to the agent

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11
Q

Initiation results from DNA ______

A

Initiation results from DNA mutation

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12
Q

The promoter does not initiate DNA damage. True/False?

A

True

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13
Q

Name an example of a promoter

A

Hormones
Inflammation/healing
Epigenetic mechanisms

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14
Q

Promoters still have an effect on cells if applied before initiation. True/False?

A

False - they have no effect if applied before initiation

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15
Q

Name 2 things promotion of tumour development results in

A
  1. Permanency of the DNA error

2. Potential for additional errors to develop

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16
Q

Initiation of tumour development can lead to what 4 cell actions?

A
  1. Increased cell proliferation
  2. Decreased cell death
  3. Decreased DNA repair
  4. Increased cell lifespan
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17
Q

The DNA mutation that occurs during initiation must be passed onto daughter cells. True/False?

A

True - Permanent change

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18
Q

Increased mitosis/cell proliferation can occur in which phase of tumour development (initiation or promotion)?

A

Initiation

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19
Q

An increased repair of DNA can occur during initiation. True/False?

A

False - decreased repair of damaged DNA

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20
Q

A _______ in the rate of cell ____ or _____ occurs during initiation of tumour development

A

A decrease in the rate of cell death or apoptosis occurs during initiation of tumour development

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21
Q

What happens in the progression phase of tumour development?

A

stepwise transformation of a benign tumor to a neoplasm and to malignancy.

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22
Q

Progression can be caused by an increased mitotic division/cell replication. True/False?

A

True

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23
Q

Inhibition of ______ can cause progression of tumour development.

A

Inhibition of apoptosis can cause progression of tumour development.

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24
Q

The removal of cell _____ restriction via promoters can cause ______ of tumour development

A

The removal of cell growth restriction via promoter can cause progression of tumour development.

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25
What is aneuploidy?
Altered karyotype
26
What is tumour heterogeneity?
Different tumour cells show distinct morphological and phenotypic profiles
27
Altered cell ____ by inactive gene expression is a factor in causing progression of tumour development
Altered cell phenotype by inactive gene expression is a factor in causing progression of tumour development
28
Name 2 forms of aneuploidy that lead to gene deletions or amplifications in tumour progression
1. Change in chromosome number | 2. Altered chromosomes via translocation or deletion
29
What carcinogenic agent can bring about neoplasia on its own without an initiator?
Oncogenic viruses
30
It requires only a single DNA error to make cells neoplastic, so time is not a factor. True/False?
False - multiple DNA errors are needed to make cells neoplastic and time IS a factor
31
Neoplasia is more common in younger animals. True/False?
False
32
Neoplasia can arise in-utero. True/False?
True
33
_ cell tumours are more common than __ cell tumours
B-cell tumours are more common than T-cell tumours
34
What type of tissue is the source of the greatest number of tumours?
Epithelium
35
Why is epithelial tissue the greatest source of tumour development?
Epithelium has the highest turnover rate of an tissue
36
If tissues have a high turnover rate, why are they more susceptible to cacinogenesis?
Higher turnover = more cell divisions = higher chance of replication errors
37
How does metastasis develop? (2 reasons)
1. Loss of intracellular adhesion | 2. Loss of apoptotic control
38
Metastasis has the ability for ______ invasion
Metastasis has the ability for vascular invasion
39
There are 3 main transmissible neoplasms. What are they?
1. Transmissible venereal tumour of dogs 2. Devil facial tumour disease 3. Transmissible haemocyte neoplasia of molluscs
40
How is devil facial tumour disease transmitted?
Biting (mouth, lips, nose)
41
Name the 3 categories of carcinogens
1. Viruses 2. Radiation 3. Chemicals
42
What type of RNA virus is a causative agent in carcinogenesis?
Retroviruses
43
What type of DNA viruses (2) can cause carcinogenesis?
1. Papillomaviruses | 2. Herpesviruses
44
Name 2 types of radiation that can cause cancer?
1. UV light | 2. Ionising radiation (X-rays)
45
What is a naturally occurring compound that can cause carcinogenesis?
Mycotoxin/aflatoxins
46
What 3 types of chemicals can lead to carcinogenesis?
1. Alkylating compounds 2. Nitrosamines 3. Aromatic amines
47
What is the mechanism behind infectious causes of cancer?
Induction of chronic inflammation
48
Chronic inflammation leads to the production of reactive _____ and ____ radicals
Chronic inflammation leads to the production of reactive oxygen and nitrogen radicals
49
Toxic nitrogen and oxygen radicals cause repetitive cell ____ and _____
Toxic nitrogen and oxygen radicals cause repetitive cell damage and repair
50
The repetitive damage and repair of cells caused by toxic oxygen and nitrogen radicals is known as........
Hyperplasia
51
Where are viral oncogenes inserted in the host?
Host genome
52
Once inserted into the host genome, viral oncogenes lead to _____ host cell oncogene ________
Once inserted into the host genome, viral oncogenes lead to uncontrollable host cell oncogene production
53
A reduction in tumour cell detection and elimination is caused by what in the host?
Viral-induced immunosuppression
54
What are xenobiotics?
Exogenous chemicals
55
What cells does papillomavirus infect in cattle?
Squamous epithelial cells
56
What is the most common actinic tumour of any animal?
Squamous cell carcinoma
57
What cell type are the most susceptible to sunlight?
Basal cells
58
Why are basal cells more susceptible to sunlight and SCC?
Basal cells have a high turnover and are more superficial
59
Name 3 triggers of apoptosis
1. Irreparable DNA damage 2. Hypoxia 3. Unrestricted mitosis
60
What is p53?
Transcription factor
61
What does p53 mediate?
Induction of BAX | Temporary mitotic cycle arrest
62
How does p53 temporarily stop mitosis cycle?
Via p21 blocking action of cyclin/CDK complexes
63
___% of human tumours have a p53 gene mutation
50% of human tumours have a p53 gene mutation
64
Cytochrome C leakage from mitochondria is an alternative pathway to.........
Apoptosis
65
Loss of cell anchorage to adjoining cells or intracellular matrix can cause what?
Apoptosis
66
The overexpression of C-myc transcription factor can cause ........?
Apoptosis
67
What are telomeres?
DNA segments at the end of chromosomes
68
What does telomerase do?
Prevents telomere shortening
69
Neoplasms can express telomerase, leading to cell immortality. True/False?
True
70
What is a proto-oncogene?
Normal gene that encodes proteins to promote mitosis
71
What are oncogenes?
Altered proto-oncogenes lacking control mechanisms
72
What are the 3 functions of proto-oncogenes?
1. Codes for growth factors and their receptors 2. Relay proteins in signal transduction pathways 3. Transcription factors
73
Oncogenes need a _____ copy to promote mitosis
Oncogenes need a single copy to promote mitosis
74
What do tumour suppressor genes encode?
Regulatory proteins that inhibit mitosis
75
What is the 'two hit hypothesis'?
Function is lost when both alleles of a gene mutate
76
What type of mutation is the first 'hit' in inherited cancers known as?
A germline mutation
77
What type of mutation is the second 'hit' in inherited cancers known as?
Somatic mutation
78
With a mutation, what acts as the promoter?
Altered genes
79
Name the 3 genetic mechanisms of tumour suppressor genes? (i.e. how is function lost)
1. Point mutations 2. Deletions 3. Recombination
80
When function of mitosis is lost due to tumour suppressor genes, the change in an organism/cell is caused by the modification of gene ________ rather than the alteration of the genetic _____.
When function of mitosis is lost due to tumour suppressor genes, the change in an organism/cell is caused by the modification of gene expression rather than the alteration of the genetic code.
81
What is known as the 'master switch' (example of tumour suppressor genes)
pRB
82
What does pRB do?
Controls cells entering into mitosis
83
What is the mechanism that allows pRB to control cells entering/exiting mitosis cycle?
Releases/inhibits E2F transcription factor, forcing the cell into the S phase. Hyperphosphorylation by cyclin/CDK complexes
84
What is p53 known as?
Master brake/genome guardian
85
What does p53 do?
Causes cell cycle arrest and induces apoptosis after DNA damage
86
What is angiogenesis?
New vessel growth
87
Tumours require sufficient blood supply to proliferate. True/False?
True
88
What happens when a tumour outgrows its blood supply?
Necrosis
89
What growth factors do malignant tumours produce?
Vascular endothelial growth factor | Fibroblast growth factor
90
What do the growth factors produced by malignant tumours induce?
Formation of capillaries

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