Radiation effects on thyroid hormono-genesis and cell proliferation in vivo

Greig, William Rattray (1970) Radiation effects on thyroid hormono-genesis and cell proliferation in vivo. PhD thesis, University of Glasgow.

Abstract

This thesis describes and compares some of the effects of external X-irradiation, iodine-131 and iodine-125 irradiations on the hormonogenetic functions of the thyroid and on cell proliferation in thin tissue. All the studies were conducted in vivo and mostly on the rat whose thyroid is a suitable model for controlled experiments observations were, however, also made on patients undergoing radiation treatment for thyrotoxicosis. The laboratory and clinical studies (conducted by myself) repeats complement and supplement observations made by others. Appropriate reference is always made when investigations by others are discussed. The thesis (composed by myself) consists of six sections. Section A is an introduction and contains a description of the microanatomy of the adult rat thyroid and the relation between minute structure and hormonogonesis and cell proliferation respectively. Section B contains a detailed account of the principles and procedures employed in the delivery and calculation of radiation doses to the rat thyroid in vivo and arising from external X-irradiation, iodine-131 or iodine-125 irradiations. The term radiation dopes refers not only to mean thyroid doses but also to inhomogeneity of done. The latter is of importance because it in shown in this section (B) that'iodine-125, in contrast to external x irradiation and iodine131 irradiation delivers about twice as much radiation to the hormonogenetic parts of the thyroid follicular cells than to their nuclei. 11 was this difference between the micro dosimetry of the three radiations which led me to compare their effects on rat thyroid hormonogenesis and on cell proliferation respectively. In Section C the studies of the effects on cell hormonogonesis are described. Cell hormonogonesis refers to thyroglobulin synthesis, thyroglobulin iodination, together with thyroglobulin composition, resorption, proteolysis and hormone release by follicular cells ln.2112. The methods used measured tritiated leuoine and radioiodine to corporation into ultracentrifugation fractions of thyroid proteins together with radiochromatographio analyses and measurement of rat blood hermetic concentrations. The studies show that most aspects of thyroid hormonogenesis are relatively radio-renistant and this includes radioeresintence to iodine..125 irradiation's. In both sections D and E the effects of X-irritation, iodine-131 or iodine-125 irradiations on follicular (and etromal) cell proliferation are deorbited. The methods used included the promotion of cell proliferation in the rat thyroid by goitrogenic stimulation together with measurements of the proportion of cells in S. phase and of the D.N.A. synthetic process itself, using tritiated thymidine. The work, including special emphasis on iodine-125 effects, shows that interruption of cell proliferation+ or impairment of cell survival, arises through the damage to the cell nucleus irrespective of damage to other parts of the cell. In Section Po all the studies and conclusions made in respect of the rat thyroid radiobiology and contained in Sections A to E respectively are brought to boar on the problems of treating thyrotoxicosie with ionising irradiations. In Section IP the structural, hormenogenetic and cell proliferative chanons in the thyrotoxic thyroid are reviewed and their relevance to the anticipated effects of X-irradiation, iodine-131 and iodine-125 irradiations on thyrotoxic cell hormonogenesia and survival are disowned. A detailed description is given of the micro dosimetry of iodine-125 in the thyrotoxic thyroid and it to included that this isotope is more likely to impair excessive hormonogenesis, without killing cells, than is iodine..131. On this basis, iodine-125 therapy wan used in two pilot studies. The restate of treatment in 62 patients prove that iodine-125 therapy in effective and further trials are in progreen.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: E M McGirr
• Keywords: Endocrinology, Nuclear physics and radiation
• Date of Award: 1970
• Depositing User: Enlighten Team
• Unique ID: glathesis:1970-73828
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jun 2019 08:56
• Last Modified: 14 Jun 2019 08:56
• URI: https://theses.gla.ac.uk/id/eprint/73828