QUANTIFYING THE FREQUENCY OF RADIOGENIC THYROID-CANCER PER CLONOGENICCELL IN-VIVO

We used quantitative cell transplantation to evaluate the frequencies of the formation of radiogenic thyroid cancer per clonogenic rat thyro id epithelial cell in vivo. Irradiation of thyroid cells with 5 Gy Cs- 137 gamma rays before transplantation significantly increased the inci dence of thyroid carcinoma formation in such grafts compared to simila r grafts of unirradiated thyroid cells. We calculated the frequencies of radiogenic cancer by subtracting cancer incidences in unirradiated groups from incidences in irradiated groups and dividing by the number of clonogens grafted. The highest observed frequencies of radiogenic thyroid cancer so calculated were 0.141 and 0.046 cancers per survivin g irradiated clonogenic cell. These cancer frequencies occurred in gra fts containing averages of three and ten clonogens per site, respectiv ely, and represent one cancer per similar to 7 and similar to 22 irrad iated clonogens. We conclude that the highest observed frequencies of radiogenic cancer are likely to be the best estimates of the ''real'' frequency per irradiated clonogen in that virtually all the methodolog ical sources of inaccuracy tend to decrease the observed frequency com pared to the ''real'' frequency. Radiogenic initiation of cancer is th us a highly common cellular event among surviving irradiated clonogeni c thyroid cells. To examine the role of endocrine-mediated tumor promo tion on the expression of radiogenic cancer, we attenuated the intensi ty of thyrotropin (TSH)-mediated tumor promotion in some groups of rec ipient animals. We found that the incidence rates for radiation-associ ated cancer were significantly higher in rats with higher serum TSH le vels compared to rats with lower TSH levels. We conclude from these da ta that (1) radiogenic thyroid cancer occurs with a high frequency and (2) chronic TSH stimulation accelerates progression of radiogenic neo plasms to overt carcinomas and promotes development of later-arising c arcinomas in grafts of unirradiated thyroid clonogens.