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Sequential Cytogenetic Changes in the Evolution of Transplanted Thyroid Tumors to Metastatic Carcinoma in the Fischer Rat¹

Department of Internal Medicine (Nuclear Medicine), University of Michigan Medical School, Ann Arbor, Michigan 48104

Inbred Fischer rats fed on an iodine-deficient diet for 16–22 months will develop goiters which will grow into tumors when transplanted subcutaneously into the flanks of other Fischer rats. We have studied the biologic behavior, histology, and the chromosomes of 1–7 generations of ten lines of these transplanted thyroid tumors and classified them into three categories: (a) Dependent tumors with a modal number of 42 chromosomes and a "normal" karyotype; follicular and papillary adenocarcinomas; slow growth; transplant take and growth rate dependent upon iodine deficiency and thyroidectomy. After the second or third generation, all tumors acquire transitional tumor characteristics. (b) Transitional tumors with a modal number of 41 chromosomes; usually missing one chromosome of "Pair No. 15" slowly growing; well-differentiated follicular or papillary carcinomas; grown in the absence of thyroidectomy and/or iodine deficiency, but take faster when these conditions are present. After the second generation, all tumors will possess some autonomous characteristics. (c) Autonomous tumors, 42–43 chromosomes but different karyotypes with marker chromosomes, and one of "Pair No. 15" missing; undifferentiated neoplasm with metastases; fast growing; no alteration of growth rate by iodine deficiency or thyroidectomy.

The dropping of one chromosome of "Pair No. 15" in the second and third types of tumors suggests that the "No. 15" chromosome under these circumstances may carry genetic information about the regulation of orderly cell growth in the Fischer rat thyroid gland.

¹ This work was supported by USPHS Grant CA-05174-07, No. 07939.

Received 2/23/67. Accepted 6/ 5/67.