Effects of humoral hypercalcemia of malignancy and gallium nitrate on thyroid C cells in nude mice: immunohistochemical and ultrastructural investigations.
Immunohistochemical and ultrastructural investigations of thyroid C cells were conducted in male nude (athymic) mice bearing a serially transplantable canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy following subcutaneous administration of gallium nitrate. The following four groups were investigated: 1) vehicle-treated non-tumor-bearing control mice; 2) non-tumor-bearing mice treated with gallium nitrate; 3) vehicle-treated hypercalcemic mice bearing CAC-8; and 4) CAC-8 tumor-bearing mice treated with gallium nitrate. Gallium nitrate-treated tumor-bearing mice had a significant decrease in serum calcium as compared with tumor-bearing controls. C cells of non-tumor-bearing mice stained intensely for calcitonin and calcitonin gene-related peptide and weakly for chromogranin A and neuron-specific enolase. In C cells of both vehicle- and gallium-treated tumor-bearing mice, immunoreactive staining was decreased for calcitonin, calcitonin gene-related peptide, and chromogranin A, whereas there was a moderate increase in staining for neuron-specific enolase. Ultrastructurally, thyroid C cells in hypercalcemic tumor-bearing control and gallium-treated mice were hypertrophic and markedly degranulated as compared with those of non-tumor-bearing controls. Hypertrophic C cells contained few mature secretory granules, a well-developed Golgi apparatus, and lamellar arrays of rough endoplasmic reticulum. There was no evidence of C-cell hyperplasia. Immunohistochemical and ultrastructural findings revealed that C cells in mice with cancer-associated hypercalcemia were primarily in the actively synthesizing phase of the secretory cycle and had diminished immunoreactivity for calcitonin, calcitonin gene-related peptide, and chromogranin A.(ABSTRACT TRUNCATED AT 250 WORDS)
Okada
H
H
Department of Veterinary Pathobiology, Ohio State University, Columbus.
Merryman
J I
JI
Rosol
T J
TJ
Capen
C C
CC
D000230:Adenocarcinoma; D000818:Animals; D005708:Gallium / Q000494:pharmacology*; D006934:Hypercalcemia / Q000209:etiology / Q000473:pathology*; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D010257:Paraneoplastic Syndromes / Q000473:pathology*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure
D005708:Gallium; C027235:gallium nitrate