Mechanisms of Carcinogenesis Flashcards
List 7 aetiological agents
- chemical
- physical
- infectious
- viral
- Bacterial/ parasitic
- inherited
- immune related
Which genes are targeted in the initiation and promotion of carcinogenesis ?`
- oncogenes
- proto oncogenes (code for proteins that help regulate cell growth and proliferation)
- tumor suppressor genes
- genes regulating apoptosis
What are two causes of carcinogenesis?
- carcinogens such as physical and chemical agents
2. ocogenes (generally used when virus is involved)
What are the 4 stages of carcinogenesis
- Initiation
- Promotion
- Progression
- Malignant conversion (sometimes)
Describe inititiation of carcinogenesis
mutations in the genetic makeup of a cell. May or may not result in cancer as cell has repair mechanisms
Describe promotion of carcinogenesis
stimulation to grow and divide faster
Describe progression of carcinogenesis
further growth
Describe malignant conversion of carcinogenesis
Doesn’t always occur. It is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as malignant degeneration of a previously existing benign tumor.
List 3 mechanisms for repair in the process of carcinogenesis
- cell cycle check points
- DNA repair
- Apoptosis
(see pge 53 of manual)
Describe proto oncogenes
- promote normal cell growth/ mitosis/ cell division
Describe tumour suppressor genes
- detect genetic damage
- stop subsequent progression of G1-S phase in mitosis
- induce DNA repair enzyme activity
Describe Direct vs. Indirect Carcinogenic mechanisms
Direct = express viral oncogenes that directly contribute to cancerous cell transformation
Indirect= chronic infection/ inflammation –> free radicals from inflammatory cells hosts mutations
How can viruses promote carcinogenesis
- virus integrates into host genome
- this integration inturrupts host’s oncogenes
- Viral products may mimic oncoproteins (e.e pappiloma virus)
List three key factors critical in the development of congenital defects
- stage of pregnancy
- Teratogen involved
- Genotype
Discuss how the stage of pregnancy determines how congenital disorders manifest
- if an embryo dies it will probably be reabsorbed
- 1st trimester is when major organogenesis occurs.
- 2nd-3rd trimester is when further development of organs and tissues (the differentiation and maturation) occurs.
This is really too complex to put of this slide
Discuss how the genotype determines how congenital disorders manifest
-usually chromosomal gene involvement
-breed predisposition
(think brachycephalic bulldogs with vertebral malformations/ polycystic kidneys in persians)
-heritable susceptibility
(what ya momma gave you)
Discuss how a chemical teratogen determines how congenital disorders manifest
- toxins
- therapeutic drug
- able to transcend placental barrier?
- concentration
Discuss how a physical teratogen determines how congenital disorders manifest
- Vit A imbalance
- Nutritional= starvation/ copper deficiency
- Physical= heat/ radiation/ vascular occlusion
Discuss how a Viral teratogen determines how congenital disorders manifest
- viruses are able to cross the placenta
- if have low pathogenicity to mother, can affect foetus without mum/baby dying
- if doesn’t kill foetus will likely have adverse affects –> hypoplasia/ vasculitis/ amputation e.g. parvovirus
Discuss how the viral teratogen involved in Akabane virus determines how congenital disorders manifest
1st tri= hydrancephaly
2nd= degeneration LMR
3rd= still birth/ abortion
Discuss how the viral teratogen involved in Border disease virus determines how congenital disorders manifest
1st= embryonic absorption 2nd= congenital defects 3rd= survival & minimal effect
Discuss how the teratogen involved in Swine fever determines how congenital disorders manifest
1st= absorption 2nd= dec growth, mummification 3rd= post natal development, dec survival
Discuss how the viral teratogen involved in parvo virus determines how congenital disorders manifest in PIGS vs. CATS
Pigs –>
1st= reabsorption
2nd= mummification
3rd= still birth/ small piglet
Cats –>
1st= reabsorption
2nd= congenital defects
3rd= cerebellar hypoplasia, retinal dysplasia
What are the two types of congenital defects neonates can suffer from
- anatomic anomalies
2. biochemical defects
Example of an anatomic anomaly
e.g. cyclopia
Example of an anatomic anomaly
Albinism= defective tyrosinase Dwarfism Haemophilia Lysosomal storage disease Dermatosporaxis= failed collagen
List the 8 categories of Anatomical Anomalies
- Failure of Development
- Failure to close/ fuse
- Failure to canalise
- Failure to separate
- Vestigial remnants & cysts
- Structure develops abnormally
- Accessory tissues abnormal
- Ectopic tissues
explain 1. Failure of Development
Agenesis= absence of an organ Aplasia= Defective development Hypoplasia= Incomplete development
Explain 2. Failure to close/ fuse
Schistosoma= abdominal midline cleft
Spina bifida= cleft in spine
Coloboma= cleft in iris
Cleft palate
Explain 3. Failure to canalise
Atresia ani= sheet of skin coveres anus
Explain 4. Failure to separate
Cyclopia= one eye
Explain 5. Vestigial remnants & cysts
Persistence of embryonic structures e.g hole in heart
Cysts= polycystic kidney
Explain 6. Structure develops abnormally
Displasia= hip displasia
Explain 7. Accessory tissues abnormal
Polydactyly= extra digits
Supernumerary teeth- more teeth
Explain 8. Ectopic tissues
tissue located in wrong place
whole organ in wrong location
