Watanabe H, Tanner M A, Domann F E, Gould M N, Clifton K H
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
Carcinogenesis. 1988 Aug;9(8):1329-35. doi: 10.1093/carcin/9.8.1329.
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 less than 50 ng iodine per g. The results confirm that radiogenic initiation is a common cellular event; one of approximately 32 surviving 5-Gy-irradiated thyroid clonogens gave rise to cancer in grafts initially containing approximately 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 approximately 11 to approximately 720 clonogens per graft site, the carcinoma frequency per grafted clonogen progressively decreased to one per approximately 920. Addition of unirradiated 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.
定量移植技术已被用于研究辐射致癌起始频率以及移植的克隆原性大鼠甲状腺上皮细胞在促进/进展过程中的细胞相互作用。移植受体通过手术切除甲状腺，并维持在每克含碘量低于50纳克的饮食中。结果证实辐射致癌起始是一种常见的细胞事件；在最初每个移植部位约含11个克隆原的移植瘤中，约32个经5 Gy照射后存活的甲状腺克隆原之一会引发癌症。数据表明促进/进展的效率与移植的受照射细胞数量呈负相关。随着每个移植部位存活的受照射克隆原数量从约11个逐渐增加到约720个，每个移植克隆原的癌发生频率逐渐降至约每920个中有1个。向移植接种物中添加未受照射的甲状腺细胞进一步抑制了辐射引发的甲状腺克隆原的促进/进展。此外，通过向移植接种物中添加未受照射的甲状腺细胞，降低了血管侵袭的概率，血管侵袭反映了由受照射的移植甲状腺克隆原产生的癌的转移潜能。对克隆原性甲状腺细胞移植44周后甲状腺切除大鼠血清中促甲状腺激素（TSH）滴度的检测表明，每个移植部位细胞数量增加时观察到的肿瘤促进/进展的抑制至少部分归因于移植来源的甲状腺激素对TSH产生的反馈抑制。局部细胞相互作用是否也参与这一抑制过程目前正在研究中。
