Carcinogens Flashcards
(30 cards)
What is the process of carcinogenesis?
3 steps
- INITIATION - mutation
- PROMOTION - increase in number
- PROGRESSION - automation. frankly malignant by acquiring capacity of invasion and metastases.
What are the three groups of carcinogens?
- Oncogenic viruses
- Radiation
- Chemicals
What are some human oncogenic viruses?
4
HPV
Epstein-barr virus
Hepatitis B
Kaposi Sarcoma Herpes virus
What types of HPV cause squamous cell papilloma?
1,2,4,7
What HPV types are associated with genital warts?
6 and 11
What do HPV 16 and 18 cause?
Squamous cell carcinoma of cervix, oral and anogenital region
In benign warts, what form is the HPV genome in?
Episomal (non-integrated)
In cancer, what form is the viral DNA in?
Viral DNA is integrated into the host genome
At what point in the viral genome is the viral DNA interrupted when HPV is inserted into the host genome?
E1/E2
What is the E2 region of HPV responsible for?
E2 region of viral DNA normally represses the transcription of E6 and E7 genes.
Therefore its interruption causes over expression of E7 and E7 proteins of HPV 16 and 18.
What does E7 do?
E7 binds to, and sequesters, the unphosphorylated form of the tumour suppressor protein pRb and DISPLACES THE E2F TRANSCRIPTION FACTORS that are normally bound by pRb.
This lets TFs go into DNA and cause cell multiplication.
E7 associates with p21 cell cycle inhibitor and prevents its inhibition of the cyclin CDK4.
What do E6 and E7 proteins do?
E6 and E7 proteins bind to and facilitate the degeneration of the p53 gene product, causing a block in apoptosis.
What is the difference btw the binding of E6/E7 proteins derived from high-risk HPV virus (16,18) compared to low risk in relation to binding Rb and p53?
High risk E6 and E7 bind to p53 and Rb with a higher affinity compared to low-risk HPV.
What tumours is Epstein barr virus associated with?
4
- Burkitts lymphoma
- B cell lymphoma
- Hodgkin disease
- Nasopharyngeal carcinoma
What does EBV infect?
epithelial cells in the oropharynx
B cells
What happens to B cells once they are infected with EBV?
they become immortalised
LMP-I1 prevents apoptosis by interacting with the bcl-2 gene
EBNA-1 gene maintains the virus in latent stage
EBNA-2 gene transactivates general viral and host cell genes important for B-cell growth
What is Burkitts lymphoma?
B cell neoplasm
Why is Burkitts lymphoma more common in Africa?
Factors such as chronic malaria favours sustained proliferation of B cells, immortalised by EBV.
What translocation mutation must occur for burkitts lymphoma?
Mutation T(8:14) occurs where c-myc is translocated to IgH gene loci on chromosome 14.
This causes overexpression of c-myc. By itself it is not sufficient for malignant transformation.
Additional mutations possibly affecting N-ras oncogene occurs in the B cells immportalised by the EBV. Together these changes lead to the emergence of a monoclonal B-cell neoplasm.
What other mutation can occur to affect B cells immortalised by EBV?
N-ras oncogene mutation
What intracellular signalling molecule is usually mutated in oral squamous cell carcinoma?
K-Ras
Why does B lymphoma often occur in patients with aids?
Weakened immune system/immunosuppression by therapy or aids.
What is the outcome of B cell lymphoma?
Multifocal B cell lymphoma in lymphoid tissue or in CNS
What is Hodgkins lymphoma? and what is a key characteristic?
Malignancy of lymphoid tissue
characterised by presence of distinctive neoplastic giant cells caused by R-S cells.
