Thyroid Tumors In Rats Research Articles

Defective thyroglobulin synthesis in an experimental rat thyroid tumor: iodination and thyroid hormone synthesis in isolated tumor thyroglobulin.

Purified rat tumor thyroglobulin from the experimental rat thyroid tumor, line 1-1C2, was studied for its thyroid hormone content after in vivo and in vitro iodination and compared with normal and desialylated normal rat thyroglobulin. Tumor thyroglobulin had a very low sialic acid and iodine content; after in vivo iodination it contained only small amounts of triiodothyronine (T3) and no detectable thyroxine (T4). After in vitro iodination with 125I it showed a distribution of T3 and T4 very similar to that of normal and desialylated normal thyroglobulin iodinated in vitro. In vitro iodination dissociated tumor and desialylated normal thyroglobulin to a greater extent than normal thyroglobulin. Tumor tissue, on the other hand, showed considerable iodinating activity in the 105,000 X g pellet when studied with exogenous acceptors. These results are compatible with a role for sialic acid in the maturation and migration of thyroglobulin to the iodination site, rpovided that the intracellular distribution of the iodinating enzymes are normal.

Incorporation of carbohydrates into abnormal thyroglobulin in an experimental rat thyroid tumor.

Previous findings indicated that in line 1–1C2 of experimental rat thyroid tumor there is decreased secretion of 19S thyroglobulin associated with a lack of incorporation of sialic acid into thyroglobulin and sialyltransferase activity in the tumor. In the present work we studied another tumor line, 1–8, in which particle bound iodopro-tein is also increased. This tumor, however, secretes an abnormal form of thyroglobulin. Soluble and digitonin-solubilized iodoproteins were examined in tumor labeled in vitro with N-acetylmannosamine, galactose, mannose, N-acetyl-glucosamine, leucine and iodine. About half of each label except galactose and N-acetyl-mannosamine was in the pellet after digitonin extraction and the remainder was evenly distrib-uted between soluble and solubilized fractions. After galactose labeling, the soluble fraction con-tained relatively more labeled protein; after N-acetylmannosamine, the pellet content was higher but most of the remainder was in the soluble fraction. The soluble and so...

Defective Thyroglobulin Synthesis in an Experimental Rat Thyroid Tumor: LACK OF MEMBRANE-BOUND SIALYLTRANSFERASE ACTIVITY

Abstract The incorporation of carbohydrates has been studied in vitro in the experimental rat thyroid tumor 1-1C2. The uptake of N-[3H]acetylmannosamine, a precursor of sialic acid, is less than 5% of that in normal thyroid gland; no label is found in 19 S thyroglobulin or its precursors either in the soluble or in the solubilized proteins. N-[3H]Acetylglucosamine is incorporated at a slower rate than in normal thyroid gland and is present in the membrane-bound thyroglobulin; there is no conversion into sialic acid in the soluble thyroglobulin of tumor as occurs in normal thyroid. [14C]Mannose and [14C]galactose are incorporated at an almost normal rate and [14C]fucose, at a subnormal rate; they are present mainly in the particle-bound proteins as ∼18 S thyroglobulin and its precursors. Measurement of sialyltransferase activity showed that, with desialylated thyroglobulin as acceptor, the 22,000–105,000 x g pellet of tumor contains ∼3% of normal sialyltransferase activity, and the soluble fraction contains ∼25% of normal activity. Desialylated fetuin and orosomucoid are generally better acceptors than desialylated thyroglobulin for tumor sialyltransferase. The findings indicate that defective thyroglobulin release and absence of incorporation of sialic acid into thyroglobulin coexist in this tumor. The very low activity of thyroglobulin-specific sialyltransferase activity in the tumor particulate fraction accounts for the failure of sialic acid incorporation into thyroglobulin and may explain the defect in thyroglobulin release.

Membrane-bound thyroglobulin in an experimental thyroid tumor of rats

Soluble and particulate iodoproteins have been studied in an experimental rat thyroid tumor (Wollman Line 1-1C 2) labeled by intraperitoneal injection of 125I-. The uptake of the tumor was very low (approx. 1% of the dose per g), and most of the radioactivity (75–95%) was particulate. The particulate iodoproteins were solubilized (10–78%) by vigorous rehomogenization and digitonin treatment; the soluble and solubilized proteins were analyzed by density gradient ultracentrifugation, microimmunodiffusion and double immunoprecipitation. Labeled 19-S thyroglobulin comprised 30–60% of the soluble iodoproteins and 10–90% of the total solubilized iodoproteins. In the iodoproteins solubilized by rehomogenization there was 10–23% 19-S at 60 min or less after injection, and most of the 125I sedimented at <6 S. This “light fraction” had a density similar to that of endoplasmic or plasma membranes and yielded 25–75% 19-S thyroglobulin when treated with digitonin. Subcellular fractionation showed that 62% of the total tumor 125I was in the “nuclear” fraction, 35% in the “microsomal” fraction and only 3% in the “mitochondrial” fraction, which should contain lysosomes. In vitro experiments failed to show non-specific adsorption of thyroglobulin as a source of membrane-bound thyroglobulin. The results suggest that in the tumor studied there is decreased synthesis of thyroglobulin and a possible defect in its release from cell membranes.

The nature of particulate thyroid proteins in an experimental rat thyroid tumor

Particulate proteins from microsomes have been studied in a rat thyroid tumor. The tumors were labeled in vivo with intraperitoneal injection of [ 14C]leucine or 125I-. A large proportion (20–50%) of the radioactivity, either 14C or 125I-, was particulate and associated with the nuclear or microsomal pellets. Proteins released by deoxycholate from microsomes were analyzed by density gradient centrifugation and tested with a rabbit anti-rat thyroglobulin serum. It was found that 60% of the proteins labeled with 125I and 30% of those labeled with 14C had a sedimentation rate of 12 S. The 12-S fractions reacted with anti-thyroglobulin serum. Density gradient centrifugation patterns of soluble proteins labeled with 14C or 125I for 30 min-18 h showed that 125I is incorporated into 19-S thyroglobulin, whereas no more than 10% of [ 14C]leucine was found in the 19-S protein. The remaining 80–90% of the radioactivity had a sedimentation rate of 3–8 S. We conclude that in this tumor a large proportion of thyroglobulin or its precursors is in the microsomes, whereas soluble thyroglobulin is low or absent possibly due to a deficiency in the mechanism for release of protein from endoplasmic reticulum.

Thin-layer gel filtration of thyroid iodoproteins. Studies on rat transplantable thyroid tumors.

Analysis of the iodine containing components in transplantable rat thyroid tumors was carried out using thin-layer gel filtration, with Sephadex G-200 Superfine, Bio-Gel P-300 and agar 7% as supporting medium. Components labeled with iodine were localized by autoradiography and quantitated by counting segments of gel removed from the plate. Gel filtration of tumor homogenates of Wollman Lines 1-1C and 1–8 revealed radioactivity at the origin (particulate iodine), a component slower than albumin (presumably iodide), and 2 relatively minor iodoprotein spots which migrated in the position of serum albumin and γ-globulin. The major radioactive component in both tumors, however, was excluded from the gel and moved with the eluant front, as does normal thyroglobulin. In sucrose density gradient centrifugation most of the radioiodine in tumor 1-1C was in a narrow 19S band characteristic of thyroglobulin. In the 1–8 tumor, however, the radioactivity was found in a zone of about 8S. These data indicate that the io...

Fine structure of thiouracil-induced transplantable thyroid tumors in non-inbred intact rats.

Electron microscopic examination of thiouracil-induced transplanted thyroid tumors reveals numerous histological patterns: 1) Tumor follicles which are characterized by normal-appearing follicular cells but differ from the host’s normal thyroid gland in their having an increased number of light cells. The light cell of the thyroid tumor contains a cytoplasmic matrix that is filled with dense, secretory-like granules. 2) Tumor follicles with grossly reduced luminal spaces. Their follicular cells have much less granular endoplasmic reticulum and a more extensive Golgi apparatus than the host’s normal thyroid cells. 3) Tumor cells which have lost the typical follicular arrangement. These cells are characterized by further alterations in their cytoplasmic elements and, in addition, possess an abundance ofmultivesicular bodies, vacuolated dense myelin-like bodies and whorls of cytoplasmic membranes. It is suggested that the alterations in the granular endoplasmic reticulum may account for the decreased product...

Thyroidal iodide transport. IX. The accumulation and metabolism of selenocyanate.

75SeCN- is concentrated by thyroid slices of various species as well as by slices of salivary or mammary glands, rat thyroid tumor, kidney and liver. Antithyroid agents markedly inhibit both total thyroidal 76Se and 75SeCN- accumulation. The major part of the thyroid 76Se is present in a form remaining at the origin in chromatography from which it can be released as 75SeCN- by OH-, CN- or mercaptoethanol. It is postulated that this 75Se is present in the form RSSeCN.(Endocrinology 79: 795, 1966)

EFFECT OF THYROIDECTOMY WITH AND WITHOUT THYROXINE REPLACEMENT ON TRANSPLANTABLE THYROID TUMORS IN RATS.

Transplanted autonomous thyroid tumors grew to a larger size in rats receiving replacement thyroxine after radioiodine thyroidectomy than in rats permitted to continue in a myxedematous state. This effect of thyroxine on neoplasm growth may not be directly on the tumor, in that no significant deiodination of thyroxine by the tumors was demonstrated. Tumor uptake of 131I per unit weight was greater in the neoplasms from the hypothyroid animals. (Endocrinology 74: 925, 1964)

Thyroidal iodide transport II. comparison with non-thyroid iodide-concentrating tissues

1. 1. The iodide-concentrating mechanisms of normal sheep thyroid, mouse submaxillary, rat-mammary and rat-thyroid tumor tissue slices have been compared. 2. 2. The tissue/medium ratio of 131Iis greater for thyroid tissue than for the other tissues under identical conditions. 3. 3. The time to attain equilibrium is 80–120 min in thyroid tissues and 30–40 min in the other three tissues. 4. 4. The tissue/medium ratio of 131I of all four tissues is reduced to half the control value at 1–3 · 10 −5 M iodide and the association constants vary from 2.7–3.3 · 10 4 M. The differences in tissue/medium ratio of 131I appear to be a function of the capacity of the system rather than the affinity for iodide ion. 5. 5. Iodide accumulation in all four tissues can be shown to be a function of the external K + concentration with half maximal stimulation of the tissue/medium ratio of 131I attained at from 0.9–2.9 · 10 −3 M of added K +. 6. 6. The cardiac glycosides, ouabain and scilliroside, depress the tissue/medium ratio of 131I in all four tissues. Scilliroside is a more potent inhibitor than ouabain by an order of magnitude. This depression can be partially reversed by the addition of 30 mequiv./l of K +, Rb + or Cs + ions.

Iodoproteins in thyroid tissue and blood of rats with a transplantable thyroid tumor.

lodoprotcins other than thyroglobulin have been detected in a transplantable rat thyroid tumor (Wollman) in which iodine compounds were labeled with I131 cither in vivo or in vitro. Two types of iodoprotein were found. One was not extractable from glass homogenized tissue by 0.15 M NaCl, and is termed “particulatc iodoprotein, ” or “P-l.” In in vivo experiments, it increased with time after I131 administration from about 15% to about 70% of the total organic iodine in the tumor. Cell particle fractionation identified this material with the “nuclear” fraction. The second type of iodoprotein was readily extracted from previously frozen (tissue slices. Unlike thyroglobulin, it was soluble in 1.89.M KH2PO4 – K2(HPO.4 sedimented slowly in the ultracentrifuge, and appeared multidispcrse on zone electrophoresis. This iodoprotein fraction comprised 3 to 9% of the soluble ido-proteins, the remainder being thyroglobulin, and its amount relative to thyro-globulin did not change with time after I131 administration. I...

Iodide trapping without organification in a transplantable rat thyroid tumor.

The present report describes a transplantable rat thyroid tumor that concentrates 40–70% of an injected dose of I131-iodidc and loses it rapidly with a half life, of 4–8 hours. The I131 in the tumor is 98–99% iodide as judged by tri-chloracetic acid solubility, chromatography and dialysis. The remainder of the I131 is organically bound and exists in the “participate” fraction. Iodide accumulation in vivo appeared to be independent of the level of thyrotropic hormone. Slices of the tumor concentrate iodide with a gradient (T/M ratio) ranging from 8 to 44.The gradient is largely abolished by various anions such as C104−, SeCN−, SCN− and by certain agents which uncouple oxidative phosphoryla-tion, such as dinitrophenol and dicumarol. Thyroxine and triiodothyronine have no significant effect on the T/M ratio at 10−4M. The defect in hormone synthesis seems to lie with the iodinating system since unlabcled thyroglobulin appears to be present. The ability to deiodinate L-diiodotyrosine has also been lost.

Iodoproteins in normal and abnormal human thyroid tissue and in normal sheep thyroid.

Two typos of iodoprotcins other than thyroglobulin have been found in normal and abnormal human thyroid tissue and in normal sheep thyroid. They are similar to, but not identical with, iodoproteins previously described in a functioning rat thyroid tumor, and were detected in tissue labeled with I131either in vivo or in vitro. One of these iodoprotcins, termed “participate iodoprotein” or “P-l” was not extractable from thyroid homogenates with 0.15 M NaCl. It comprised from 1 to 6% of the organic radioiodinc in normal thyroids and in several abnormal thyroid tissues, but was 37% in a follicular carcinoma. The second iodoprotein, termed “S-l iodoprotein,” was soluble in 0.15 M NaCl, but differed from thyroglobulin in other physical properties. It was more soluble than thyroglobulin in phosphate buffer, scdimented more slowly in the ultracentrifuge, and had a faster electrophoretic mobility. It comprised from 1 t o 7% of the extractable organic radioiodinc in normal and in a wide variety of abnormal thyroids...

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Induction of thyroid tumors in rats by a low iodine diet.

Induction of thyroid tumors in rats by a low iodine diet.

The Experimental Development and Metabolism of Thyroid Gland Tumors

Publisher Summary This chapter discusses that the occurrence of spontaneous tumors of the thyroid gland in rats and mice is exceedingly rare. However, thyroid gland tumors have been produced in these laboratory animals by several different methods. There is ample indirect proof that such tumors occur when the thyroid gland tissue is subjected to continuous prolonged stimulation by increased amounts of thyrotropin evoked by a deficiency of circulating thyroid hormone. The chapter reviews that the conditions most favorable to the development of independent or autoiromous thyroid gland tumors have not yet been completely apprehended with the support of the available studies, the view that much variation occurs in experimentally produced thyroid tumors in both rats and mice. A long but also variable induction period exists. Although, the reasons for the decreased capacity to collect and bind iodine that occurs in experimentally produced thyroid gland tumors remain largely unknown and since, most cancers of the thyroid gland in man have also lost much of their ability to collect iodine compared to that of the normal thyroid gland it seems reasonable to conclude that quite similar explanations may exist for these functional changes of thyroid gland neoplasm's that occur during thyroid gland carcinogenesis in both animals and man.

Activity of thyroid of cold-exposed rats evaluated by I131 uptake and histometric studies.

ArticleActivity of Thyroid of Cold-Exposed Rats Evaluated by I131 Uptake and Histometric StudiesBoris Catz, Ihsan El Rawi, and Ernest GeigerBoris CatzFrom the University of Southern California, Departments of Medicine, Biochemistry and Nutrition, and Pharmacology, Los Angeles, California, Ihsan El RawiFrom the University of Southern California, Departments of Medicine, Biochemistry and Nutrition, and Pharmacology, Los Angeles, California, and Ernest GeigerFrom the University of Southern California, Departments of Medicine, Biochemistry and Nutrition, and Pharmacology, Los Angeles, CaliforniaPublished Online:01 Jul 1953https://doi.org/10.1152/ajplegacy.1953.174.1.29MoreSectionsPDF (677 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByActivity of the hypothalamic-pituitary-thyroid axis during exposure to coldPharmacology & Therapeutics, Vol. 41, No. 1-2The Influence of Dietary Iodine and Enviromental Temperature on the Activity of Mitochondria in Liver and Kidney9 October 2009 | Zeitschrift für Tierphysiologie Tierernährung und Futtermittelkunde, Vol. 40, No. 1-6The effects of cold exposure and hibernation on the thyroidal activity of Mesocricetus auratusGeneral and Comparative Endocrinology, Vol. 5, No. 3REFERENCESChemistry and Physiology of the Thyroid-stimulating HormoneInduction of thyroid tumors in rats by a low iodine dietCancer, Vol. 8, No. 2 More from this issue > Volume 174Issue 1July 1953Pages 29-32 Copyright & PermissionsCopyright © 1953 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1953.174.1.29PubMed13065489History Received 18 February 1953 Published online 1 July 1953 Published in print 1 July 1953 Metrics