Which agent is a cell-cycle specific antimetabolite?

• A. Mercaptopurine
• B. Asparaginase
• C. Procarbazine
• D. Thiopeter

Answer: (A)

Antimetabolites work by mimicking normal nucleotides and blocking DNA synthesis, with many of them most active when cells are in the S phase of the cycle. Mercaptopurine is a purine analog that, once inside the cell, is activated to thioinosinic acid and disrupts purine nucleotide synthesis and incorporation into DNA and RNA. This interference directly affects DNA replication, so its cytotoxic effect is greatest when cells are dividing and synthesizing DNA, making it a cell-cycle specific antimetabolite. By contrast, asparaginase depletes asparagine rather than inhibiting nucleotide synthesis, and procarbazine and thiotepa are alkylating-type agents that act across multiple cell-cycle phases rather than being confined to S phase.