Crucial role of thyroid hormone in x-ray-induced neoplastic transformation in cell culture.

Abstract

Incubation of mouse embryo fibroblasts (C3H/10T 1/ 2) in media depleted of thyroid hormone for 1 wk rendered the cells completely resistant to the transforming action of an X-ray dose, 4 grays, that yields transformation frequencies (number of foci per surviving cells) of .apprxeq. 10-3 in media supplemented with triiodothyronine (T3) (1 nM). Studies on the timing of the additions or removal of the hormone indicate that T3 was maximally effective when added 12 h before irradiation and that progression from the time of irradiation to the appearance of foci (6 wk) was independent of the presence or absence of the hormone. The dependence of X-ray-induced transformation on the concentration of T3 in the medium was virtually the same as that for augmentation of Na+,K+-ATPase activity. The latter effect was used as a measure of T3 induction of protein synthesis. A further indication of the involvement of protein synthesis in the process is the abolition of T3- and X-ray-dependent transformation by cycloheximide at a concentration (100 ng/ml) that inhibits 50% of protein synthesis. Thyroid hormone apparently induces the synthesis of a host protein that is an obligatory participant in X-ray-mediated transformation.