Causes of Neoplasia

Question 1

Intrinsic Factors

Answer 1

DNA-damaging metabolites
○ E.g. ROS in organic acids
Cause DNA damage (lesions) leading to mutations in critical cancer-related genes resulting in neoplasia

Question 2

Extrinsic Factors

Answer 2

Chemical environmental factors
Physical environmental factors
Oncogenic viruses

Question 3

Mutagen

Answer 3

Agents which causes DNA damage and gives rise to DNA mutation
Many mutagens are also carcinogens

Question 4

Carcinogen

Answer 4

Agents which can cause cancer
Some carcinogens have unknown mechanism of action so may not be mutagens

Question 5

ROS

Answer 5

Reactive Oxygen Species
Unstable molecule that contain oxygen and easily reacts with other molecules in a cell
Build-up in cells may cause damage to DNA and RNA
Free radicals

Question 6

Chemical Environmental Agents

Answer 6

Direct-acting chemical carcinogens
○ Effective in the form in which they enter the body
Indirect-acting chemical carcinogens
○ Procarcinogens
○ Most carcinogens
○ Require metabolic activation by enzymes such as CYP450 in hepatic microsomes

Question 7

Physical Environmental Agents

Answer 7

(Complete carcinogens)
Initiate and promote oncogenesis
Ionising radiation
○ Direct DNA damage
○ ROS generation - highly reactive
UV radiation (sunlight)
○ Formation of hallmark pyrimidine dimers which are mutagenic
○ ROS generation - highly reactive

Question 8

Oncogenic Viruses

Answer 8

Viruses that cause cancer
Direct and in-direct mechanisms

Question 9

Proto-oncogene

Answer 9

Unmutated genes which are involved in growth factor pathways
Allow a cell to proliferate

Question 10

Oncogene

Answer 10

Mutated gene
Promotes autonomous growth
Uncontrolled proliferation
Codes for specific oncoproteins

Question 11

Oncoproteins

Answer 11

Result of oncogene coding
Devoid of internal regulatory elements
Cells expressing them are freed from normal check point and control

Question 12

Direct mechanisms of Oncogenic Viruses

Answer 12

Dominant oncogene mechanism
Insertional Mechanism
Hit and run mechanism

Question 13

Dominant oncogene mechanism

Answer 13

Mutated gene in viruses that drives tumour development
Either obtained from host animal cells or within viral genome

Question 14

Dominant oncogene mechanism derived from host cell

Answer 14

• By incorporating a cellular proto-oncogene in the genome of the infecting virus and subsequently transmitting the oncogene to new animal cells
• Once oncogene becomes part of viral genome, expression is no longer subject to normal cellular controls
  Uncontrolled production of onco-proteins from viral oncogene drives cell proliferation and then carcinogenesis
• E.g. Sarcoma virus, Feline Leukaemia Retrovirus

Question 15

Dominant oncogene mechanism derived from within viral genome

Answer 15

• Endogenous oncogene
• Not derived from host target cell genome
• Encodes for specific protein that inhibits the tumour suppressor protein
• E.g. Canine Papillomavirus, E6-E7

Question 16

Insertional Mechanism

Answer 16

Viruses that do not possess their own oncogene
Instead activate the suppression of target cells oncogene
By inserting specific viral DNA in host cells
Results in unregulated production of target cells oncoprotein responsible for neoplasm formation
E.g. avian leukosis virus

Question 17

Hit-and-Run Mechanism

Answer 17

• Viral genome causes neoplasm by transient (non-permanent) residence in target cells
• Presence of virus necessary but typically no longer detectable in tumour
• E.g. Bovine papillomaviruses

[Insertional and dominant oncogene mechanisms are permanent]

Question 18

In-direct Mechanisms of Oncogenic viruses