Carcinogens

Question 1

What is the process of carcinogenesis?

3 steps

Answer 1

1. INITIATION - mutation
2. PROMOTION - increase in number
3. PROGRESSION - automation. frankly malignant by acquiring capacity of invasion and metastases.

Question 2

What are the three groups of carcinogens?

Answer 2

1. Oncogenic viruses
2. Radiation
3. Chemicals

Question 3

What are some human oncogenic viruses?

4

Answer 3

HPV
Epstein-barr virus
Hepatitis B
Kaposi Sarcoma Herpes virus

Question 4

What types of HPV cause squamous cell papilloma?

Answer 4

1,2,4,7

Question 5

What HPV types are associated with genital warts?

Answer 5

6 and 11

Question 6

What do HPV 16 and 18 cause?

Answer 6

Squamous cell carcinoma of cervix, oral and anogenital region

Question 7

In benign warts, what form is the HPV genome in?

Answer 7

Episomal (non-integrated)

Question 8

In cancer, what form is the viral DNA in?

Answer 8

Viral DNA is integrated into the host genome

Question 9

At what point in the viral genome is the viral DNA interrupted when HPV is inserted into the host genome?

Answer 9

E1/E2

Question 10

What is the E2 region of HPV responsible for?

Answer 10

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.

Question 11

What does E7 do?

Answer 11

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.

Question 12

What do E6 and E7 proteins do?

Answer 12

E6 and E7 proteins bind to and facilitate the degeneration of the p53 gene product, causing a block in apoptosis.

Question 13

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?

Answer 13

High risk E6 and E7 bind to p53 and Rb with a higher affinity compared to low-risk HPV.

Question 14

What tumours is Epstein barr virus associated with?

4

Answer 14

1. Burkitts lymphoma
2. B cell lymphoma
3. Hodgkin disease
4. Nasopharyngeal carcinoma

Question 15

What does EBV infect?

Answer 15

epithelial cells in the oropharynx

B cells

Question 16

What happens to B cells once they are infected with EBV?

Answer 16

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

Question 17

What is Burkitts lymphoma?

Answer 17

B cell neoplasm

Question 18

Why is Burkitts lymphoma more common in Africa?

Answer 18

Factors such as chronic malaria favours sustained proliferation of B cells, immortalised by EBV.

Question 19

What translocation mutation must occur for burkitts lymphoma?

Answer 19

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.

Question 20

What other mutation can occur to affect B cells immortalised by EBV?

Answer 20

N-ras oncogene mutation

Question 21

What intracellular signalling molecule is usually mutated in oral squamous cell carcinoma?

Answer 21

K-Ras

Question 22

Why does B lymphoma often occur in patients with aids?

Answer 22

Weakened immune system/immunosuppression by therapy or aids.

Question 23

What is the outcome of B cell lymphoma?

Answer 23

Multifocal B cell lymphoma in lymphoid tissue or in CNS

Question 24

What is Hodgkins lymphoma? and what is a key characteristic?

Answer 24

Malignancy of lymphoid tissue

characterised by presence of distinctive neoplastic giant cells caused by R-S cells.

Question 25

What are pts with Hep B virus likely to be at risk of developing?

Answer 25

Hepatocellular carcinoma (HCC)

Question 26

How can Hep B cause cancer?

Answer 26

Liver cell injury - mutations in mitotically active cells causing inactivation of p53.

Production of HBx - disrupts normal growth control of cells by transcriptional activation of general host cell oncogenes e.g. insulin like growth factor II.

Hbx binds to p53 and stops it suppressing growth of cells.

Question 27

What type of virus is human t cell leukaemia virus type 1?

Answer 27

RNA retro virus

Question 28

What tumours is Human T cell leukaemia virus type 1 associated with?

Answer 28

T cell leukaemia/lymphoma

Question 29

How is human t cell leukaemia virus type 1 transmitted?

Answer 29

sexual intercourse, blood or breast feeding by transmission of infected T cells.

Question 30

What is the pathology of Human T cell leukaemia virus type 1?

Answer 30

Leukaemia occurs in 1% of people after a latent period of 20-30 yrs.

Contains tax gene, essential for viral replication.

Tax gene activates transcription of general host genes such as one for the cytokines IL-2, and its receptor, allowing for autocrine system of proliferation.

self-sufficiency with growth factors.