A cancer patient receives prophylactic allopurinol before a course of chemotherapy. Which of the following is the main purpose of doing this? (LQ)
|A||Facilitate host cell detoxification of the chemotherapeutic drug, thereby reducing host cell toxicities|
|B||Inhibit the potential for DNA repair, by topoisomerases, that otherwise might lead to chemotherapy failure|
|C||Potentiate the action of a nitrogen mustard or nitrosourea to bind to purine moieties in DNA strands|
|D||Reduce the risk of hyperuricemia and its main consequences that can occur with a massive cell kill.|
a. Hyperuricemia is associated with many cancers and is a common outcome of massive cell kills induced by chemotherapeutic drugs. The uric acid is derived from cellular purine degradation, eventually formed from hypoxanthine and xanthine via xanthine oxidase, the key enzyme that is inhibited by allopurinol.
b. Renal damage (and other damage, such as gout) is due to uric acid’s poor solubility in body fluids, especially at low pH.
c. Allopurinol has no effect on the P450 system or on cellular transitions from one phase of the cell cycle to another. There is no effect on DNA synthesis or repair, or any direct cytoprotective effect on myeloid or other tissues.