resistance to 6-thioguanine (6-TG) of some cell lines resistant to 6-mercaptopurine (6-MP) have led some investigators to assume that 6-TG and 6-MP havesimilar or identicalmetaboliceffects. This cross-resistance can probably be explained on the basis of the resistance mechanism, which has been so thoroughly investigated by Brock man and his associates (2). Since it now ap pears that both 6-MP a...

Evidence reported earlier, indicating that the tumor-inhibitory properties of 6thioguanine resulted from the incorporation of this guanine analog into the nucleic acids of the tumor, was supported by the following additional findings: (a) susceptible tumors showed maximum response to treatment initiated at any time during the rapidgrowth phase; (b) incorporation of thioguanine into tumor-cell n...

Individualizing drug therapy by the use of pharmacogenomics offers the opportunity to improve drug efficacy, reduce adverse side effects, and provide cost-effective pharmaceutical care. 6-mercaptopurine (6-MP), 6-thioguanine (6-TG) and azathioprine (AZA) are widely prescribed cytotoxic and immunosuppressive drugs used in the therapy of acute leukaemia, inflammatory bowel diseases, allograft rej...

The recessive deficiency in thiopurine methyltransferase (TPMT), caused by germ-line polymorphisms in TPMT, can cause severe toxicity after mercaptopurine. However, the significance of heterozygosity and the effect of the polymorphism on thioguanine or in the absence of thiopurines is not known. To address these issues, we created a murine knockout of Tpmt. Pharmacokinetic and pharmacodynamic s...

The recessive deficiency in thiopurine methyltransferase (TPMT), caused by germ-line polymorphisms in TPMT, can cause severe toxicity after mercaptopurine. However, the significance of heterozygosity and the effect of the polymorphism on thioguanine or in the absence of thiopurines is not known. To address these issues, we created a murine knockout of Tpmt . Pharmacokinetic and pharmacodynamic ...