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We have investigated the effect of inhibitors of ADP-ribosyltransferase on the cytotoxicity of a range of S-phase acting drugs. Co-administration of 3 mM 3-aminobenzamide (3AB) potentiated the cytotoxicity of TG 2-fold, but had no effect on the cytotoxicity of HU, FdUrd or araC. Higher concentrations of benzamides (e.g. 10-20 mM 3AB) produced a G1-specific cell cycle blockade. This treatment prevented cells entering S-phase DNA synthesis and consequently protected against the cytotoxicity of the same S-phase acting drugs. Thus, using different treatment regimens with 3AB, it was possible to either potentiate or protect against the cytotoxicity of TG.

Type

Journal article

Journal

Biochem Pharmacol

Publication Date

01/06/1988

Volume

37

Pages

2155 - 2160

Keywords

Benzamides, Cell Survival, Cells, Cultured, Cytarabine, DNA Repair, Dose-Response Relationship, Drug, Drug Interactions, Hydroxyurea, Interphase, Poly(ADP-ribose) Polymerase Inhibitors, Thioguanine