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Busulfan is an alkylating agent that contains 2 labile methanesulfonate groups attached to opposite ends of a 4-carbon alkyl chain. Once busulfan is hydrolyzed, the methanesulfonate groups are released and carbonium ions are produced. These carbonium ions alkylate DNA, which results in the interference of DNA replication and RNA transcription, ultimately leading to the disruption of nucleic acid function. Specifically, its mechanism of action through alkylation produces guanine-adenine intrastrand crosslinks. This occurs through an SN2 reaction in which the relatively nucleophilic guanine N7 attacks the carbon adjacent to the mesylate leaving group. This kind of damage cannot be repaired by cellular machinery and thus the cell undergoes apoptosis.
Busulfan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands – directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn leads to a miscoding of DNA. Alkylating agents are cell cycle-nonspecific and work by three different mechanisms, all of which achieve the same end result – disruption of DNA function and cell death.
Mainly Hepatic. Busulfan is predominantly metabolized by conjugation with glutathione, both spontaneously and by glutathione S-transferase (GST) catalysis.
Signs of overdose include allergic reaction, unusual bleeding or bruising, sudden weakness or unusual fatigue, persistent cough, congestion, or shortness of breath; flank, stomach or joint pain; pronounced nausea, vomiting, diarrhea, dizziness, confusion, or darkening of the skin, chills, fever, collapse, and loss of consciousness.
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Questions? Call our customer API support number 1-(800)-881-8210.
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