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 language | English (US) |
|---|---|
| Pages (from-to) | 1329-1335 |
| Number of pages | 7 |
| Journal | Carcinogenesis |
| Volume | 9 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1988 |
Funding
The authors are indebted to Jane Barnes, Dyan Nagle, Mary Burkard and Joan Mitchen for excellent technical assistance. This work was supported in part by American Cancer Society grant RD179 and US Department of Energy contract DE-AC02-84ER60195 to K.H.C. and National Cancer Institute (DHHS) grant R23-CA35464 to M.A.T. The authors received partial salary support from National Cancer Institute grant P30-CA14520 to the University of Wisconsin Clinical Cancer Center.
ASJC Scopus subject areas
- Cancer Research
