Carcinogenesis

Question 1

Polycyclic hydrocarbons

Answer 1

INDIRECT. Highly carcinogenic, found in cigs, require metabolic activation by Cytochrome P450 in the liver. If CYP1A1 is mutant = highly inducible = increased conversion of polycyclic hydrocarbons = increased risk for lung cancer in light smokers. Lung & bladder cancer.

Question 2

AA and azo dyes

Answer 2

INDIRECT. toxic in the liver - causes liver cancer, activated by CytP450.

Question 3

B-naphthylamine

Answer 3

INDIRECT. Polycyclic hydrocarbon that causes bladder tumor instead of liver tumor because carcinogen activated by urinary glucoronidase

Question 4

CYP1A1 mutation

Answer 4

results in highly inducible cytochrome p450 which results in increased conversion of polycyclic hydrocarbons to carcinogen and thus leads to increased lung cancer risk even for light smokers

Question 5

aflatoxin B1

Answer 5

INDIRECT. Produced by fungus on corn, acts alongside hep B to cause hepatocellular carcinoma. Causes china/africa to have higher rates of liver cancer than US.

Question 6

HTLV-1

Answer 6

RNA retrovirus that causes ATLL. (adult T cell leukemia)

Question 7

HPV

Answer 7

causes cervical cancer, & squamous cell carcinoma through use of viral proteins. HPV E6 degrades p53 (loss of apoptosis, growth arrest, DNA repair) and stimulates expression of TERT (inc. telomerase). HPV E7 binds RB causing loss of RB function = no growth arrest; and inhibits p21 = no growth arrest.

Question 8

HPV E6

Answer 8

degrades p53 (increased proliferation, genomic instability, loss of apoptosis, increased mutations), stimulates TERT expression (increases telomerase)

Question 9

HPV E7

Answer 9

binds RB causing loss of RB function and inhibits p21. = loss of growth arrest

Question 10

EBV (epstein barr)

Answer 10

causes lymphomas and nasopharyngeal carcinoma. Viral protein LMP-1 activates NFKB (TF) and Jak/STAT = increased proliferation. Also activates Bcl2 = anti-apoptosis.

Question 11

Hepatitis C

Answer 11

assc with hepatocellular carcinoma by forming a complex with RB protein and targeting for degradation. Loss of RB = loss of growth arrest.

Question 12

LMP-1

Answer 12

EBV viral protein that activates NFKB (TF), Jak/STAT, and Bcl2. = increased proliferation, anti-apoptosis.

Question 13

H pylori

Answer 13

assc with gastric carcinoma and lymphoma due to constant inflammation which prevents B-cells from dying by apoptosis. (MALTomas)