Borek C, Guernsey D L, Edelman I S
IARC Sci Publ. 1982(39):269-78.
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.
辐射和化学物质的直接致癌潜力在细胞培养中是可证明的，在细胞培养中宿主介导的影响并不占主导。这些系统提供了研究调节肿瘤转化因素的机会。诸如类视黄醇等试剂可调节后期事件，并抑制转化的表达以及12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯的促癌作用。甲状腺激素在早期事件即转化起始中发挥作用。培养基中的三碘甲状腺原氨酸（T3）与单细胞的相互作用是暴露于X射线和苯并[a]芘后启动转化的先决条件。当克隆的仓鼠胚胎细胞和小鼠10T 1/2细胞在不含甲状腺激素的血清培养基中（甲状腺功能减退条件下）培养并暴露于3或4 Gy X射线时，尽管细胞存活和细胞生长不受甲状腺激素水平影响，但未观察到转化。在暴露于X射线前12小时向培养基中添加10 - 12M至10 - 7M的T3会导致与T3剂量相关的转化频率，在10 - 10M时达到峰值。该曲线与钠钾ATP酶诱导的曲线相似。在辐射时添加T3会导致较低的转化频率；如果在辐射后添加则未观察到转化。T3在起始过程中的作用不能被反式T3模拟，并且加入100 ng环己酰胺可消除该作用。数据表明，T3使细胞具备转化能力的作用涉及一种细胞“转化蛋白”的合成。正在进行的实验表明，仅在存在T3的情况下，暴露于1微克/毫升苯并[a]芘才会导致转化。在甲状腺功能减退条件下，未观察到转化。
