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The Metabolism of 9-Butyl-6-thioguanine in Normal and Neoplastic Tissues^*

( Life Sciences Division, Stanford Research Institute, Menlo Park, California)

The metabolism of 9-butyl thioguanine (9-BTG)¹ was studied in normal tissues and the Ehrlich ascites tumor with and without pretreatment with azaserine. The study of the distribution and metabolism of the drug was facilitated by the synthesis of 9-butyl-6-thioguanine-8-C¹⁴.

The results showed that 9-BTG was rapidly cleared from the blood, rapidly catabolized, and that the metabolites were rapidly excreted in the urine. Pretreatment with azaserine resulted in a longer retention of radioactivity in the acid-soluble fraction of the tissues.

Radioactivity was also found in the lipide fraction of the tissues. It was confirmed that 9-BTG was neither dealkylated nor incorporated into nucleic acids.

Treatment with toxic doses produced bone marrow depression with a terminal agranulocytosis.

^* This work was supported in part by Contract No. SA-43-ph-3068 with the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health, and in part by grants from the United States Public Health Service (CY-4551) and the Gustavus and Louise Pfeiffer Research Foundation.

A preliminary report of this work has been made (Proc. Am. Assoc. Cancer Res., 3:333, 1962).

¹ Abbreviations used: 9-BTG, 9-butyl-6-thioguanine; 9-BTG-8-C¹⁴, 9-butyl-6-thioguanine-8-C¹⁴; BW, water-saturated n-butanol; PA, n-propanol-1 M ammonium hydroxide (1:1); TCA, trichloroacetic acid.

Received 6/15/62.