Hormones and the single cell: a relationship prerequisite for transformation

The direct oncogenic potential of radiation and chemicals is demonstrable in cell cultures, where host-mediated influences do not prevail. These systems afford the opportunity of investigating factors that modulate neoplastic transformation. Agents such as retinoids modulate late events and inhibit the expression of transformation and the promotional effects of 12-O-tetradecanoylphorbol-13-acetate. Thyroid hormones play a role in early events, in initiation of transformation. Interaction of triiodothyronine (T3) in a culture medium with single cells is a prerequisite for the initiation of transformation following exposure to X-rays and to benzo[a]pyrene. When cloned hamster embryo cells and mouse 10T 1/2 cells are maintained in a medium containing serum without thyroid hormones (hypothyroid conditions) and exposed to 3 or 4 Gy X-rays, no transformation is observed, although cell survival and cell growth are unaffected by thyroid hormone level. Supplementation of the medium with 10-12M to 10-7M T3 12 h before exposure to X-rays results in a transformation frequency related to the dose of T3, with a peak at 10-10M. The curve is similar to that induced by Na/K ATPase. Addition of T3 at the time of radiation results in a lower transformation frequency; if it is added after radiation no transformation is observed. The effect of T3 in the process of initiation is not mimicked by reverse T3 and is abolished by addition of 100 ng cyclohexamide. The data suggest that the effect of T3 in rendering the cell competent to transform involves synthesis of a cellular 'transforming protein'. Ongoing experiments indicate that exposure to 1 microgram/ml benzo[a]-pyrene results in transformation only in the presence of T3. Under hypothyroid conditions, no transformation is observed.