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Biochemical and Carcinostatic Effects of 2'-Deoxythioguanosine^*

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

The - and ß-anomers of 2'-deoxythioguanosine were studied in mice, in comparison with thioguanine riboside and thioguanine, as to host toxicity, capacity to become incorporated into nucleic acid nucleotides, and therapeutic effects on mammary tumors of C3H mice. They were also tested on several thioguanine-resistant ascites cell tumors of mice. The ß-anomer, thioguanine riboside, and thioguanine appear to be of approximately equal toxicity on a molar basis. The -anomer was found to be much less toxic. The ß-anomer was superior to thioguanine or the other nucleosides in the treatment of C3H mammary tumors.

In two types of resistance to thioguanine, that resulting from lack of the phosphoribosylpyrophosphorylase for the formation of nucleotide from thioguanine and that resulting from poor capacity for conversion of ribotides to deoxyribotides, the deoxyribonucleosides of thioguanine appear to have utility.

^* 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 United States Public Health Service Grant No. CY-4551.

Received 12/16/63.