Inhibition of carcinoma formation and of vascular invasion in grafts of radiation-initiated thyroid clonogens by unirradiated thyroid cells

Hiromitsu Watanabe, Martin A. Tanner, Frederick E. Domann, Michael N. Gould, Kelly H. Clifton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Quantitative transplantation techniques have been employed to study radiogenic cancer initiation frequency and cell interactions during promotion/progression in grafted clonogenic rat thyroid epithelial cells. The graft recipients were surgically thyroidectomized and maintained on a diet containing <50 ng iodine per g. The results confirm that radiogenic initiation is a common cellular event; one of ∼ 32 surviving 5-Gy-irradiated thyroid clonogens gave rise to cancer in grafts initially containing ∼11 clonogens per transplantation site. The data demonstrate that the efficiency of promotion/progression is inversely related to grafted irradiated cell number. As the number of transplanted surviving irradiated clonogens was increased progressively from ∼11 to ∼720 clonogens per graft site, the carcinoma frequency per grafted clonogen progressively decreased to one per∼920. Addition of un-irradiated thyroid cells to the transplant inocula further suppressed promotion/progression of radiation-initiated thyroid clonogens. Furthermore, the probability of vascular invasion, a reflection of metastatic potential in carcinomas which arose from irradiated grafted thyroid clonogens, was reduced by addition of unirradiated thyroid cells to the transplant inocula. Assays of thyroid stimulating hormone (TSH) titers in the sera of thyroidectomized rats 44 weeks after transplantation of clonogenic thyroid cells indicate that the suppression of neoplastic promotion/progression observed with increased numbers of cells per graft site is due at least in part to feed-back inhibition of TSH production by thyroid hormone of graft origin. Whether local cellular interactions are also involved in this inhibitory process is currently under investigation.

Original languageEnglish (US)
Pages (from-to)1329-1335
Number of pages7
JournalCarcinogenesis
Volume9
Issue number8
DOIs
StatePublished - Aug 1988

ASJC Scopus subject areas

  • Cancer Research

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