Assessment of Rat Thyroid as a Radiobiological Model the Effects of X-irradiation on Cell Proliferation and DNA Synthesisin Vivo

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Abstract
The cell population of the normal adult rat thyroid gland, a closed population, shows very little proliferation as measured by sequential changes in thyroid weight, cell density, chemical DNA and RNA and by total uptake of tritiated thymidine (3H-T) into cell DNA or by cell-labelling indices (L.I.). In contrast, administration of a continuous goitrogenic challenge (0·1 per cent methylthiouracil as drinking fluid and a low iodine diet) induces, after a lag phase of 2 days, a 2–3-fold increase in thyroid weight, the maximum weight being attained within 28 days of the goitrogenic challenge. During thyroid growth the cell density falls about 10 per cent; chemical DNA rises with gland weight but slightly less than chemical RNA; and both the uptake of 3H-T and L.I. parallel the rate of change of DNA content. Doses of 100, 500 or 1000 rads x-rays given to the normal rat thyroid produce latent cell damage; there is an impairment of weight increase during a subsequent goitrogenic challenge, and this is related to the dose of x-rays; irradiation has no influence on cell density but results in a 2–3-fold increase above control values in both the uptake of 3H-T and L.I. The peak uptakes of 3H-T and L.I. after irradiation are not clearly dose-dependent, but they do coincide with the time when thyroid growth is arrested or slowed by previous irradiation. The rat thyroid, growing under the influence of a 28-day goitrogenic regime is a closed dividing population. If allowance is made for initial weight and the weight increase not due to cell division, the system can be used to measure the effects of irradiation on mammalian thyroid cell survival in vivo. Special features of the system include an intrinsic restricted capacity of the cell population to undergo more than an average of one or two divisions and the advantage that stromal cells may be distinguished from follicular cells. Evidence is produced to suggest that stromal cells might be more radio-resistant than follicular cells. The increased peak rate of DNA synthesis in x-irradiated rat thyroid in which growth is promoted by a goitrogenic challenge appears to be due to the accumulation of cells damaged in G1 at S-phase. The cells appear to accumulate not so much because the generation time is slowed but because of their special built-in restricted capacity to multiply.