Synergistic induction of sister-chromatid exchanges in lymphocytes from normal subjects and from patients under cytostatic therapy by inhibitors of poly(ADP-ribose)polymerase and antitumour agents.

The effects of nicotinamide on SCE rates induced in vitro by chlorambucil (CBC or melphalan (MELPH) or mitomycin C (MMC) was studied. The combined treatments with either CBC or MELPH or MMC and nicotinamide showed the potentiating ability of the latter drug. Theophylline and MELPH were also found to act synergistically on the induction of SCEs. In a combined in vivo and in vitro study, lymphocytes taken from 7 cancer patients who had been given cytoxan by injection 3 h before, were treated with nicotinamide or diphylline (DP) in vitro, and found to have synergistically increased exchange rates. This has implications for interpreting the repair processes involved, for monitoring drug combinations that synergistically damage DNA in vivo and in vitro and for identifying interindividual variation in the response to the treatment.