Desoxyribonucleic Acid (DNA) Synthesis in the Radiated and Stimulated Thyroid Gland

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Abstract
Nuclear changes and DNA synthesis of thyroid cells of rats in early and late post I131 radiation were explored. Tritiated thymidine and radio-autography were used to identify nuclei which were synthesizing DNA, and Feulgen staining and microspectrophotometry were used to measure amounts of DNA in individual nuclei. Thiouracil was used as a stimulus. Although obvious destruction of cells with rapid loss of function may not occur, subtle damage is demonstrable by newer methods. Thyroids which retained 1.5-2 [mu]c of a dose of I131 (2640 rads), when stimulated early after radiation, displayed some transient impairment in capacity for DNA synthesis, followed by a supramaximal response at 2 months. A stimulus at 8 months produced DNA synthesis and increased thyroidal weight comparable to nonradiated glands, but unusual variations in nuclear DNA and volume persisted. Large and sometimes bizarre nuclear forms were usually synthesizing DNA. In contrast, thyroids which retained 15-20 [mu]c (26,400 rads), without obvious thyroidal destruction, lost the ability to synthesize DNA and to hypertrophy when stimulated. Later, the ability to synthesize DNA and to increase in weight remained impaired. Marked variation in individual DNA content among cells persisted. Some nuclei contained amounts of DNA greater than 2 times the diploid value at which cell division should have taken place. The observations presumably explain the common ultimate functional failure of human thyroids years after a seemingly ideal therapeutic dose of I131. The ultimate loss of thyroidal function results from failure of replication based on failure of DNA synthesis which occurs after larger doses of I131, or thwarted cell division which occurs after somewhat smaller doses.