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RNA cleavage and inhibition of protein synthesis by bleomycin

  1. Author:
    Abraham, A. T.
    Lin, J. J.
    Newton, D. L.
    Rybak, S.
    Hecht, S. M.

  2. Author Address

    Univ Virginia, Dept Chem, Mccormick Rd, Charlottesville, VA 22901 USA Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA Univ Virginia, Dept Biol, Charlottesville, VA 22901 USA NCI, Lab Biochem Physiol, Div Basic Sci, Frederick, MD 21702 USA NCI, Frederick Canc Res & Dev Ctr, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA Hecht SM Univ Virginia, Dept Chem, Mccormick Rd, Charlottesville, VA 22901 USA
    1. Year: 2003
  2. Journal: Chemistry & Biology
    1. 10
    2. 1
    3. Pages: 45-52
  4. Type of Article: Article
  1. Abstract:

    Bleomycin is a clinically used antitumor antibiotic long thought to function therapeutically at the level of DNA cleavage. Recently, it has become clear that bleomycin can also cleave selected members of all major classes of RNA. Using the computer program COMPARE to search the database established by the Anticancer Drug Screening Program of the National Cancer Institute, a possible mechanism-based correlation was found between onconase, an antitumor ribonuclease currently being evaluated in phase III clinical trials, and the chemotherapeutic agent bleomycin. Following these observations, experimentation revealed that bleomycin caused tRNA cleavage and DNA-independent protein synthesis inhibition in rabbit reticulocyte lysate and when microinjected into Xenopus oocytes. The correlation of protein synthesis inhibition to the previously reported site-specific RNA cleavage caused by bleomycin supports the thesis that RNA cleavage may constitute an important element of the mechanism of action of bleomycin.

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