The ability of macrophages to induce drug-resistant variants was studied in an in vitro macrophage-tumor cell coculture system utilizing the hypoxanthine-guanine phosphoribosyl transferase locus as measured by resistance to 6-thioguanine. Tumor cells of mouse mammary tumor line 66 were sensitive to macrophage induction of thioguanine resistance as shown by an increase in the frequency of thiogu...

SUMMARY Mice treated simultaneously with 1-0-D-arabinofuranosyl-cytosine (ara-C) and 6-thioguanine (6-TG) were protected from the lethal effects of 6-TG. No protection was afforded if ara-C was given 16 hr before the 6-TG. DNA synthesis in mouse bone marrow was immediately depressed to 3 to 12% of that of control in various experiments, after treatment with ara-C, 10 to 20 mg/kg; it then reboun...

thioguanine is attributable to incorporation of the anti metabolite into deoxyribonucleic acid (DNA) and that re sistance may be the result of a lower capacity for such in corporation; and (d) Paterson (17, 19), using a 6-mercap topurine-resistant Ehrlich carcinoma, proposed a decreased rate of transport of drug across the cell membrane as a possible mechanism for the resistant character of thi...

The tumor-inhibitory jxitency of combinations of the cupric chelate of kethoxal bis(thiosemicarbazone) [Cu(II)KTS] with several compounds that cause inhibition of the synthesis of DNA by different biochemical mechanisms was assessed in Sarcoma 180 ascites cells. Cu(II)KTS prolonged the survival time of tumor-bearing mice, whereas neither cupric chloride, copper stéarate,nor kethoxal bis(thiose...

With great interest, we have read the updated ECCO consensus on the treatment of Crohn's disease.1 Being highly interested in research on the clinical use of thiopurines, we feel that several additional commentsmay give opportunity to a more balanced, evidence-based conclusion on the discarded use of 6-thioguanine as an alternative thiopurine. Firstly, the authors state that 6-thioguanine is th...

AIMS The thiopurines, azathioprine, 6-mercaptopurine and 6-thioguanine are one of the success stories of chemotherapy. They are effective immunosuppressants and anti-cancer agents and are prescribed increasingly to treat inflammatory diseases. Although their metabolism has been studied in detail, the optimal use of thiopurines has been guided predominantly by clinical experience and the precise...

6-Thioguanine (6-TG) was administered to 15 patients with acute leukemia and to 9 with solid tumors in 32 experiments, as part of Phase I testing of 6-TG. 6-TG and metabolites were measured by labeling the 6-TG with radiosulfur. The levels of 6-TG and metabolites were measured in blood and urine after p.o. and i.v. dosage. Incorporation into DNA and RNA of the bone marrow was measured. Blood le...

3D culture 658 4E-BP1 424 5-FU 1846 6-thioguanine 269 7q34 722 A2

Several 9-alkyl, 6-thiopurines have been reported to have more favorable therapeutic indexes than do the parent drugs, 6mercaptopurine (MP) and 6-thioguanine (TG). Some of these compounds were reported to be active against cells in culture resistant to 6-thiopurines, and it has been assumed that their mechanisms of action may differ from those of TG and MP. 9(n-Butyl)-6-thioguanine was essentia...