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- and ß-2'-Deoxythioguanosine in Extracts of Murine and Human Tissues1
Life Sciences Research, Stanford Research Institute, Menlo Park, California 94025, and Department of Medicine, University of Southern California, Los Angeles, California
Conditions for the conversion of
-2'-deoxythioguanosine (
-TGdR) and ß-2'-deoxythioguanosine (ß-TGdR) to nucleotides were studied in extracts of murine and human tissues. These methods were applied to assays for nucleotide formation in a series of extracts from solid tumors, neoplastic bone marrows, and normal bone marrows obtained from human patients. The results show that most of such tissue extracts can phosphorylate ß-TGdR, and an appreciable percentage of extracts from the neoplasms can also phosphorylate
-TGdR. The extracts of normal bone marrows, with one exception, did not phosphorylate
-TGdR. The DNA polymerase of several tumors incorporated nucleotides of
-TGdR and ß-TGdR into DNA. These results encourage the view that such tests on tumor biopsies might permit the selection of tumors with sensitivity to the deoxythioguanosines. It appears that an earlier finding in murine tissues, in which
-TGdR was converted to nucleotide and inhibited the tumors without marrow toxicity may carry over to human patients.
1 This work was supported by Contract No. PH 43-65-575 with the Cancer Chemotherapy National Service Center, National Cancer Institute, NIH.
Received 7/ 8/68. Accepted 11/11/68.
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