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The Incorporation of 6-Thioguanine into RNA Fractions and Its Effect on RNA and Protein Biosynthesis in Mouse Sarcoma 180 Ascites Cells¹

Department of Pharmacology, The George Washington University School of Medicine, Washington, D. C. 20005

We examined the incorporation of 6-thioguanine into the RNA of Sarcoma 180 to determine the relative distribution of this drug in the various RNA fractions.

6-Thioguanine-³⁵S was recovered from ribosomal RNA, transfer RNA, and rapidly labeled RNA (probably messenger RNA) as the intact compound. The incorporation of the analog into microsomal RNA was inhibited by actinomycin D and was enhanced by azaserine.

6-Thioguanine caused an immediate decrease of uridine labeling of the cytoplasmic ribosomal RNA and transfer RNA; at the same time, protein biosynthesis was inhibited. Maximal inhibition was observed 3 to 4 hr after the administration of the base analog. No inhibition of uridine labeling of the rapidly labeled cytoplasmic RNA was evident until 3 hr after drug treatment. The possible role of macromolecular effects of thioguanine on growth inhibition is discussed.

¹ This work was supported by USPHS Research Grant CA 02978 from the National Cancer Institute, NIH, Bethesda, Md. 20014.

² Present address: Department of Biochemistry and Pharmacology, Tufts University School of Medicine, Boston, Mass. 02111.

³ Present address: Department of Biological Chemistry, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45219.

⁴ To whom reprint requests should be sent.

Received 5/18/72. Accepted 1/29/73.

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