A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
An 8-year-old boy is brought to the physician because of a 1-day history of severe left hand pain. He has had similar painful episodes in the past that required hospitalization. Physical examination shows pale conjunctivae. There is tenderness on palpation of the wrist and the small joints of the left hand. Peripheral blood smear shows crescent-shaped erythrocytes. He is started on a pharmacologic agent that is known to cause macrocytosis. This drug causes an arrest in which of the following cell cycle phases?
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A
M phaseIncorrect. M-phase arrest is the mechanism of vinca alkaloids (vincristine, vinblastine) and taxanes, not hydroxyurea.
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B
S phaseCorrect. Hydroxyurea inhibits ribonucleotide reductase, depleting deoxynucleotides and arresting cells in S phase — the mechanism behind the macrocytosis it produces.
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C
G2 phaseIncorrect. G2-phase arrest is characteristic of bleomycin, not hydroxyurea.
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D
G1 phaseIncorrect. G1-phase arrest is seen with some growth factor and cyclin inhibitors but is not the mechanism of hydroxyurea.
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E
G0 phaseIncorrect. G0 is the quiescent, non-dividing phase; hydroxyurea acts by inhibiting ribonucleotide reductase and arresting actively cycling cells in S phase, not by holding cells in G0.
↑ Tap an answer to reveal the reasoning
Answer: B. Recurrent painful crises with crescent-shaped (sickled) erythrocytes on smear and anemia in a child define sickle cell disease (HbSS). The disease-modifying drug that causes macrocytosis is hydroxyurea — a ribonucleotide reductase inhibitor that blocks conversion of ribonucleotides to deoxyribonucleotides, depleting the dNTP pool needed for DNA synthesis. By inhibiting DNA synthesis, hydroxyurea arrests cells in the S phase of the cell cycle.
Hydroxyurea's clinical benefit in sickle cell disease comes from inducing fetal hemoglobin (HbF) expression in erythroid precursors, which dilutes HbS and prevents polymerization. The S-phase arrest also slows red cell maturation, producing macrocytic red cells (elevated MCV) as a marker of compliance and biologic effect.
Clinical pearl: hydroxyurea is also used in essential thrombocythemia, polycythemia vera, and some myeloproliferative disorders — always via S-phase arrest from ribonucleotide reductase inhibition.
**Why each option:**
**A.** M-phase arrest is the mechanism of vinca alkaloids (vincristine, vinblastine) and taxanes, not hydroxyurea.
**B.** Hydroxyurea inhibits ribonucleotide reductase, depleting deoxynucleotides and arresting cells in S phase — the mechanism behind the macrocytosis it produces.
**C.** G2-phase arrest is characteristic of bleomycin, not hydroxyurea.
**D.** G1-phase arrest is seen with some growth factor and cyclin inhibitors but is not the mechanism of hydroxyurea.