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The Effects of Thyroxine on Nucleic Acid and Protein Metabolism in Mouse Thyrotropic Pituitary Tumors^*

( John Collins Warren Laboratories, Huntington Memorial Hospital, Harvard University, Massachusetts General Hospital, and James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, Massachusetts)

The effects of thyroxine on the incorporation of glycine-1-C¹⁴ into ribonucleic acid (RNA), deoxyribonucleic acid (DNA), acid-soluble purines, and protein were compared in nine thyroxine-inhibitable ("dependent") and twelve autonomous thyrotropic pituitary tumors in LAF₁ mice.

Orotic acid-6-C¹⁴ was given to all mice prior to thyroxine (or control) treatment, to provide, in the case of RNA and DNA, an index of the effect of thyroxine less variable than glycine incorporation alone; viz., the ratio incorporation of glycine into purines/incorporation of orotic acid into pyrimidines (RSA purines/RSA pyrimidines).

In dependent tumors, thyroxine treatment was associated with a significant reduction in this ratio—56 per cent in the case of RNA and 35 per cent in the case of DNA. This apparent inhibition of nucleic acid synthesis may reflect at least in part an inhibition of purine synthesis, since thyroxine treatment was associated with a 51 per cent reduction in the incorporation of glycine into acid-soluble purines in one of two subpassages of the dependent tumor strain studied. Incorporation of glycine into protein was not demonstrably affected in these short-term experiments.

In autonomous tumors, thyroxine did not demonstrably affect RNA, DNA, purine, or protein synthesis, as measured by incorporation of glycine, or by the ratio RSA purines/RSA pyrimidines.

It appears that the acquisition of autonomy by mouse thyrotropic tumors is associated with a loss of susceptibility of nucleic acid synthesis to inhibition by thyroxine.

^* This is publication No. 1120 of the Cancer Commission of Harvard University. This investigation was supported by research grants C-558 and C-3424 from the National Institutes of Health, U.S. Public Health Service, and by a post-sophomore fellowship grant, PX-322-7, from the Division of General Medical Sciences, U.S. Public Health Service.

Received 11/13/62.