2015 Antineoplastics

I. Crosslinking agents

Mechanism (alkylating agents)

Alkylating agent mechanism

  1. Must be (or become) strong electrophiles (as charged molecules generally do not cross the blood/brain barrier very well)

  2. Attack on cell nucleophiles: -SH of protein, -N- of protein or DNA base (esp. N7 position of guanine), =O of DNA base or phosphate

  3. DNA damage includes:
    1. crosslinking (esp. if bifunctional agent)
    2. miscoding of DNA bases (esp. G-T pairing)
    3. DNA strand breakage (depurination)
Although crosslinking agents are dependent upon proliferation, these agents ARE NOT CELL CYCLE SPECIFIC (i.e., they are CCNS) because the alkylation reactions that initiate cell death can occur during any phase of the cell cycle. However, primary toxicity occurs in late G1 and S phase, with cell cycle arrest occuring in G2.
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Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 11-apr-15 9:39 AM