Question

Two of your friends are studying the mechanism of action of Compound X, known to cause lung

cancer. The primary route of exposure is through inhalation for those who work with the

compound. A reactive metabolite formed by only by a P450 enzyme is thought to be

responsible for this carcinogenic effect.

a. The first friend used a chamber to expose mice to the Compound X via inhalation. They

chose an exposure level that was one hundred times higher than what is expected in the

workplace. Afterwards, they extracted lung samples and found the reactive metabolite.

They argued that this proved that lung P450 was making this metabolite, and therefore was

responsible for the observed lung cancer. You disagreed. Provide an alternative hypothesis.

(2 pts)

b. The other friend made microsomes

from mouse heart, liver, brain,

kidney and lung. They then

performed an assay to see if the

P450s in those microsomes would

produce the toxic metabolite. Their

result is on the right. They argued

that these data proved that the

observed lung cancer must be due to

a liver, not a lung P450.

You were not convinced, noting two

major problems with this experiment. What were they? (4 pts)

c. What experiment might help decide if lung or liver P450s are responsible for the toxic

metabolite?