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Alkylating agents

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Alkylating agents are substances used in cancer treatment that interferes with the division of cells.

Alkylating agents are a class of antineoplastic or anticancer drugs which act by inhibiting the transcription of DNA into RNA and thereby stopping the protein synthesis. 

Mechanism of action of Alkylating agents

Alkylating agents substitute alkyl groups for hydrogen atoms on DNA, resulting in the formation of cross links within the DNA chain and thereby resulting in cytotoxic, mutagenic, and carcinogenic effects.  This action occurs in all cells, but alkylating agents have their primary effect on rapidly dividing cells which do not have time for DNA repair.  Cancer cells are among the most affected because they are among the most rapidly dividing cells.  However, hematopoetic, reproductive, and endothelial cells also divide rapidly which accounts for the common side effects of the alkylating agents:  anemia, pancytopenia, amenorrhea, impaired spermatogenesis, intestinal mucosal damage, alopecia, and increased risk of malignancy.  The end result of the alkylation process results in the misreading of the DNA code and the inhibition of DNA, RNA, and protein synthesis and the triggering of programmed cell death (apoptosis) in rapidly proliferating tumor cells.  The alkylating agents are generally separated into six classes:

  1. The nitrogen mustards [mechlorethamine, cyclophosphamide, ifosfamide, melphalan and chlorambucil]
  2. Ethylenamine and methylenamine derivatives [altretamine, thiotepa]
  3. Alkyl sulfonates [busulfan]
  4. Nitrosoureas [carmustine, lomustine]
  5. Triazenes [dacarbazine, procarbazine, temozolomide]
  6. The platinum-containing antineoplastic agents [cisplatin, carboplatin, oxaliplatin], which are referred to as platinum coordination complexes.  These antineoplastic drugs are usually classified as alkylating agents, although they do not alkylate DNA, but cause covalent DNA adducts by a different means.

Also see acid-base balance


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