Hypersensitivity to clinically useful alkylating agents and radiation in poly(ADP-ribose) polymerase-deficient cell lines

Cancer Commun. 1990;2(12):401-7. doi: 10.3727/095535490820873958.

Abstract

Mutant V79 Chinese hamster cell lines, deficient in poly(ADP-ribose) polymerase activity, were previously shown to be significantly resistant to etoposide, a topoisomerase II inhibitor, and hypersensitive to camptothecin, a topoisomerase I inhibitor (Chatterjee, S.; Trivedi, D.; Petzold, S.J.; Berler, N.A. Mechanism of epipophyllotoxin-induced cell death in poly(adenosine diphosphate-ribose) synthesis-deficient V79 Chinese hamster cell lines. Cancer Res. 50:2713-2718, 1990 and Chatterjee, S.; Cheng, M.F.; Trivedi, D.; Petzold, S.J.; Berger, N.A. Camptothecin hypersensitivity in poly(adenosine diphosphate-ribose) polymerase-deficient cell lines. Cancer Commun. 1:389-394; 1990). We have now demonstrated hypersensitivity of these mutant cell lines, designated ADPRT 54 and ADPRT 351, to a variety of antitumor agents including melphalan, BCNU, mitomycin, and bleomycin. They are also hypersensitive to UV- and x-irradiation. These mutants, however, are significantly resistant to the topoisomerase II-targeted DNA intercalators, Adriamycin and m-AMSA. Our results strongly suggest that inhibition of poly(ADP-ribose) polymerase could be useful to potentiate the cytotoxicity of a variety of currently available antitumor drugs.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkylating Agents / pharmacology*
  • Amsacrine / pharmacology
  • Animals
  • Bleomycin / pharmacology
  • Carmustine / pharmacology
  • Cells, Cultured
  • Cricetinae
  • Dimethyl Sulfoxide / pharmacology
  • Doxorubicin / pharmacology
  • HEPES / pharmacology
  • In Vitro Techniques
  • Melphalan / pharmacology
  • Mitomycins / pharmacology
  • Poly(ADP-ribose) Polymerases / physiology*
  • Radiotherapy*
  • Ultraviolet Rays

Substances

  • Alkylating Agents
  • Mitomycins
  • Amsacrine
  • Bleomycin
  • Doxorubicin
  • Poly(ADP-ribose) Polymerases
  • Melphalan
  • HEPES
  • Carmustine
  • Dimethyl Sulfoxide