Thymidine-cisplatin vs thymidine-carboplatin interactions in human T-cell acute leukemia

Thymidine is shown to sensitize JM human T-cell acute leukemia cells to cisplatin killing in vitro with dose modifying factors of 1.72, 1.62, and 1.76 at 200, 500, and 1000 micrograms thymidine/ml x 24 h. The magnitude of thymidine-cisplatin sensitization increases with longer thymidine exposures (500 micrograms/ml) up to 16 h but is not further increased at 24 h. For a 25 h thymidine exposure, enhancement is greater for cisplatin (3 micrograms/ml x 1 h) starting 12-24 h into the thymidine exposure vs starting at 0-8 h (p less than or equal to 0.0004). Results are precisely the same for simultaneous studies using carboplatin except that (1) thymidine enhances carboplatin cytotoxicity more than cisplatin killing, (2) enhancement of carboplatin killing varies little with the timing of carboplatin administration during a 25 h thymidine exposure. These findings are discussed relative to their clinical applicability.