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Precursor Cytogenetic Changes of Transplantable Thyroid Carcinoma in Iodine-deficient Goiters¹

Department of Internal Medicine (Nuclear Medicine), University of Michigan Medical Center, Ann Arbor, Michigan 48106

The cytogenetic changes in the thyroid cells of 199 Fischer rats are reported here. Fifty-eight rats were maintained on a normal iodine diet and 141 rats were maintained on an iodine-deficient diet for 7–25 months. Rats were sacrificed in groups of two to ten at two-week to one-month intervals; their thyroid cells were grown in cell culture and prepared for chromosomal analyses. An average of 4.5 ± 0.5% aneuploidy was found in the thyroid cells of control rats and no structural abnormalities. In the iodine-deficient rat, the percent of aneuploid cells increased with time of iodine deficiency from that of the control to 46.4 ± 5.1% at 21–25 months of iodine deficiency.

The percent cells with 41 chromsomes increased from 1.1 ± 0.05 in the control to 21.3 ± 6.1 at 21–25 months of iodine deficiency. Similarly, the percent of cells with 43 chromosomes changed from 0.15 ± 0.1 to 12.9 ± 3.9%. The number of marker chromosomes was also significantly increased with prolonged time of iodine deficiency. Ninety to 100 percent of the cells with 41 chromosomes have the same chromosome missing: "one of pair #15." After one year of iodine deficiency, 5% of the rats acquired a new modal number in their thyroid glands. The weight of the thyroid gland increased from an average of 6.7 ± 0.3 in the control to 183.2 ± 7.4 mg/100 gm body weight at 21–25 months of iodine deficiency. Similarly, the weight of the pituitary was about more than twice that of the control after more than 14 months of iodine deficiency.

The implication of these chromosomal changes to the production of neoplastic thyroid tumors from iodine-deficient goiters is discussed.

¹ This work was supported by USPHS Grant CA-05174-07, Training Grant NIH CA-5134-06, and USPHS 5-SO1-FR-538306.

Received 9/ 8/67. Accepted 12/28/67.