potassium-perchlorate and Hyperplasia

The perchlorate discharge assay (PDA) is potentially of high diagnostic value to distinguish between direct and indirect thyroid toxicity mechanisms, provided that standard treatment times are established and positive controls yield reproducible results. Therefore the PDA was evaluated after 2 and/or 4 weeks of treatment with positive control compounds in rats. Phenobarbital, Aroclor 1254 and beta-naphthoflavone (indirect toxic mechanism) enhanced thyroidal radioiodide accumulation, and the administration of potassium perchlorate had no effect on thyroid: blood (125)I ratio. Phenobarbital caused follicular cell hypertrophy and hyperplasia in the thyroid and centrilobular hypertrophy in the liver, without effects on serum triiodotyronine (T(3)), thyroxine (T(4)) levels. Thyroid-stimulating hormone (TSH) levels were moderately increased. Propylthiouracil (direct toxic mechanism) caused severe thyroid follicular cell hypertrophy and hyperplasia, reduced serum T(3) and T(4) levels and increased serum TSH levels, and reduced thyroidal radioiodide accumulation; perchlorate administration significantly reduced thyroid: blood (125)I ratio, demonstrating an iodide organification block. Potassium iodide (direct toxic mechanism) virtually blocked thyroidal radioiodide accumulation, without significant effects on serum T(3), T(4), and TSH levels and a microscopic correlate for higher thyroid weights. Thus, positive controls yielded reproducible results and we conclude that both the 2- and 4-week PDA is suitable to distinguish between direct and indirect thyroid toxicity mechanisms.

Topics: Animals; beta-Naphthoflavone; Chlorodiphenyl (54% Chlorine); Hyperplasia; Hypertrophy; Iodine Radioisotopes; Male; Perchlorates; Phenobarbital; Potassium Compounds; Potassium Iodide; Propylthiouracil; Rats; Rats, Wistar; Reproducibility of Results; Sensitivity and Specificity; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine; Toxicity Tests; Triiodothyronine

Although in both human and experimental pathology ras mutations have been related to the origin and progression of follicular-cell tumours, reports differ considerably with respect to the frequency of such mutations. The present paper reports, using direct sequencing, the incidence of Ki-ras mutations (codons 12 and 13) in follicular-cell carcinomas of the thyroid gland in Wistar rats induced by administration of radioactive iodine and potassium perchlorate. Direct sequencing revealed no mutations in the amplified gene segment of any of the 72 carcinoma samples studied. This absence of mutations agrees with some and is in sharp contrast with other previous reports in the literature, both for experimental animals and in studies of human thyroid follicular-cell carcinoma. Our results suggest that Ki-ras activation via mutations at codons 12 and 13 is neither a constant event nor an early event in the development of rat thyroid follicular-cell carcinoma.

Topics: Adenocarcinoma, Follicular; Animals; Codon; DNA Mutational Analysis; DNA, Neoplasm; Female; Genes, ras; Hyperplasia; Iodine Radioisotopes; Perchlorates; Potassium Compounds; Precancerous Conditions; Rats; Rats, Wistar; Thyroid Gland; Thyroid Neoplasms

This study was designed to investigate the histologic changes in goitrogen-induced thyroid growth of the rat. The animals were orally treated by 1% potassium perchlorate except the controls and were sacrificed in intervals ranging from 1 to 12 months. The thyroid weight increased progressively along the treatment and after 2 months showed a diffuse homogenous hypertrophy and hyperplasia of follicular cells, decreased amount of colloid and increased vascularity. After sixth month of treatment true nodules appeared with complex morphology.

Topics: Animals; Female; Hyperplasia; Hypertrophy; Perchlorates; Potassium; Potassium Compounds; Random Allocation; Rats; Rats, Inbred Strains; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule