Causes of Neoplasia Flashcards
What are Intrinsic factors of neoplastic transformation
DNA damaging metabolites- such as ROS
DNA damage -> mutations in critical cancer-related genes -> neoplasia
what are extrinsic factors for neoplastic transformation (3)
Chemical or physical agents
Oncogenic Viruses
Difference between carcinogen and mutagen
Mutagen= agent that gives rise to DNA damage
Carcinogen= substances that can cause cancer, mechanism may be unknow (could be a mutagen or not)
What are direct acting chemical carcinogens
Effective in the form that they enter the body
What are indirect-acting chemical carcinogens
Procarcinogens- require metabolic activation by enzymes, such as cytochrome P450 in hepatic microsomes
What is a complete carcinogen
causes initiation and promotion
Effect of ionising radiation
Physical environmental agent
causes direct DNA damage and ROS generation
Effect of UV radiation
Causes formation of hallmark pryimidine dimers (mutagenic) and ROS production
What are oxygen reactive species (ROS)
Highly reactive molecules which cause many types of DNA damage
What is a proto-oncogene
Unmutated gene
frequently involved in growth factor pathways
When mutated it leads to uncontrolled cell proliferation
What is an oncogene
mutated gene
Promoted autonomous growth of oncoprotein
What are oncoproteins
have ability to promote cell growth in absence of normal growth promotion signal
Bear mutation, devoid of internal regulatory elements
Cells expressing them are freed from normal check point and control
Dominant oncogene mechanism of oncogenic viruses
Direct Mechanism, permanent
A mutated gene in viruses drives tumour development
The mutation is obtained by:
1. host animal cells (e.g. sarcoma virus, Feline Leukaemia retrovirus)
2. Viral genome (endogenous)(e.g. canine papillomavirus, E6-E7)
Insertional mechanism of oncogenic viruses
Direct Mechanism, permanent
Typical of viruses that do not possess their own oncogene
Neoplasm caused by insertion of viral DNA that in return activated target cell oncogene
e.g. avian leukosis virus
hit-and-run mechanism of oncogenic viruses
Viral genome cause neoplasm by transient (not persistent) residence in target cells
Virus necessary but no longer detectable in tumour
E.g. Bovine Papillomavirus
