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Potentiation of Cell Killing by Inhibitors of Poly(Adenosine Diphosphate-Ribose) Synthesis in Bleomycin-treated Chinese Hamster Ovary Cells¹

Groupe "Radiochimie de l'ADN," Institut Gustave-Roussy, 94805 Villejuif Cedex, France

Bleomycin-treated Chinese hamster ovary cells synthesize poly(adenosine diphosphate-ribose) in a reaction which is dose and time dependent. Treatment with two poly(adenosine diphosphate-ribose) synthesis inhibitors (3-aminobenzamide and 3-methoxybenzamide) slows down the restoration of DNA structure in bleomycin-treated cells, as shown by nucleoid sedimentation. When added in the culture medium, these inhibitors increase the cell sensitivity towards bleomycin, in the case of both exponentially growing and stationary cells. In control experiments, plateau-phase cells treated with bleomycin can recover by repairing efficiently the potentially lethal damage; this type of repair is mostly suppressed in the presence of the poly(adenosine diphosphate-ribose) synthesis inhibitors.

¹ This work was supported by grants from Centre National de la Récherche Scientifique, Institut National de la Santé et de la Recherche Médicale, and a research contract from Institut Gustave-Roussy (82 D 9).

² To whom requests for reprints should be addressed.

Received 7/31/84. Accepted 11/ 9/84.