We have evaluated the effect of allopurinol on the hematopoietic toxicity of 6-mercaptopurine in rabbits by studying the development of neutropenia in animals that received only 6-mercaptopurine and in those that received both drugs. The studies showed that, rather than demonstrat ing any potentiation of 6-mercaptopurine toxicity, allopurinol protected the animals, as evidenced by less weight l...

The effect on granulopoiesis of 6-mercaptopurine alone, and in combination with allopurinol, was studied in mice using an in vitro colony-forming assay for granulocytic progenitor cells. The combination of 6-mercaptopurine and allopurinol pro duced significantly greater suppression of de novo granulo poiesis than did 6-mercaptopurine alone. Allopurinol in very high doses was found to be myelosu...

Leukemia L1210 ascites tumor cells sensitive to inhibition by 6-mercaptopurine were observed to metabolize hypoxanthine-8-C14 and 6-mercaptopurine-S36 to ribonucleotide derivatives in vivo. Hypoxanthine-8-CH extensively labeled adenylic and guanylic acids of L1210 nucleic acids. Soluble enzyme preparations from L1210 ascites cells catalyzed the reactions of adenine, guanine, 8-azaguanine, hypox...

BACKGROUND 6-Mercaptopurine and its prodrug azathioprine are effective medications for refractory inflammatory bowel disease. However, use of these drugs has been limited by concerns about their toxicity. Colonic delivery of azathioprine may reduce its systemic bioavailability and limit toxicity. AIM To determine the bioavailability of 6-mercaptopurine after administration of azathioprine via...

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 ...

The purine anti-metabolite 6-mercaptopurine is one of the most widely used drugs for the treatment of acute childhood leukemia and chronic myelocytic leukemia. Developed in the 1950s, the drug is also being used as a treatment for inflammatory diseases such as Crohn's disease. The antiproliferative mechanism of action of this drug and other purine anti-metabolites has been demonstrated to be th...

BACKGROUND Patients with acute lymphoblastic leukemia are often treated with 6-mercaptopurine, and those with homozygous deficiency in thiopurine S-methyltransferase (TPMT) enzyme activity have an extreme sensitivity to this drug as a result of the accumulation of higher cellular concentrations of thioguanine nucleotides. We studied the metabolism, dose requirements, and tolerance of 6-mercapto...

1. The formation of adenosine 5'-phosphate, guanosine 5'-phosphate and inosine 5'-phosphate from [8-(14)C]adenine, [8-(14)C]guanine and [8-(14)C]hypoxanthine respectively in the presence of 5-phosphoribosyl pyrophosphate and an extract from Ehrlich ascites-tumour cells was assayed by a method involving liquid-scintillation counting of the radioactive nucleotides on diethylaminoethylcellulose pa...

BACKGROUND AND AIMS High concentrations of methylated thiopurine metabolites, such as 6-methyl mercaptopurine, are associated with hepatotoxicity during administration of the conventional thiopurines azathioprine or 6-mercaptopurine in IBD patients. Metabolization of the non-conventional thiopurine 6-thioguanine does not generate 6-methyl mercaptopurine. Hence, the aim of our study was to evalu...