A series of experiments were performed to eludicate the
tissue-specific action of 2-naphthylamine and the results are as
follows:-
a) incubation of human liver microsomes with 2-naphthylamine plus
NADPH and UDP-glucoronic acid resulted in the formation of
hydroxy-2-nepphthylamine-beta-1-gluconyl pyranoside (NHNGP).
b) human bladder tissue incubated with 2-naphthylamine formed
acetyl-2-naphthylamine.
c) NHNGP, 2-naphthylamine and N-acetyl-2-naphthylamine did not bind to
DNA nor did these compounds stimulate DNA repair in hepatocytes.
d) in the pH range 5.5-6.5, the N-glycosidic bond in NHNGP was readily
hydrolysed. One of the products was strongly reactive with DNA.
Questions
1. why was it necessary to determine whether or not 2-naphthylamine or
its derivatives bind to DNA or stimulate DNA repair?
2. Why ere microsomes, UDP-glucoronic acid and NADPH included in the
experiments? Describe how the agent 2-naphthylamine might be
metabolised in the liver.
3. What is the significance of the pH range 5.5-6.5?
4. Considering all the observations, explain why you think that
2-naphthylamine results in bladder cancer and not liver carcinoma?
5. Write a report of no more than 500 words entitled "carcinogens in
the workplace".