Mothersill C, O'Brien A, Seymour C B
Dublin Institute of Technology, Ireland.
Radiat Environ Biophys. 1990;29(3):213-23. doi: 10.1007/BF01210524.
Radiation is known to be carcinogenic to humans but attempts to demonstrate the process using human tissue culture models have met with little success. In the present study explants were established from urothelium and exposed to radiation and a range of chemical carcinogens, suspected promotor or metabolic agents. The resulting outgrowth was monitored for growth rate, proliferating epithelial fraction and development and differentiation of endothelial cells in culture. The results indicate that enhanced growth of epithelial cells can be seen when cultures are irradiated in the presence of various nitrosamines, benzo(a)pyrene or aniline. Radiation alone reduced the overall growth area measured but several proliferative foci developed on the resulting outgrowth. Their ultrastructural appearance reveals that they carry severe mitochondrial damage and exposure of treated cultures to metabolic inhibitors confirms that their respiration is defective. Endothelial cells proliferated over the surface of the epithelial monolayer and both the number and the degree of differentiation of the endothelial cells increased with increasing dose up to 10 Gy. While the cultures are not immortalised by the treatment, it appears that the epithelial cells have an extended lifespan (division capacity) and that a subpopulation has undergone a number of premalignant changes. Changes in endothelial cell proliferation also occur.
已知辐射对人类具有致癌性，但试图利用人体组织培养模型来证明这一过程的尝试收效甚微。在本研究中，从尿路上皮建立外植体，并使其暴露于辐射以及一系列化学致癌物、疑似促癌剂或代谢剂中。对培养过程中产生的生长物进行生长速率、增殖上皮细胞比例以及内皮细胞发育和分化情况的监测。结果表明，当培养物在各种亚硝胺、苯并(a)芘或苯胺存在的情况下接受辐射时，上皮细胞的生长会增强。单独辐射会减小测量的总体生长面积，但在产生的生长物上会形成几个增殖灶。它们的超微结构外观显示，这些增殖灶存在严重的线粒体损伤，并且将处理过的培养物暴露于代谢抑制剂中证实其呼吸存在缺陷。内皮细胞在上皮单层表面增殖，并且内皮细胞的数量和分化程度随着剂量增加至10 Gy而增加。虽然处理并未使培养物永生化，但上皮细胞似乎具有延长的寿命（分裂能力），并且一个亚群已经发生了一些癌前变化。内皮细胞增殖也会发生变化。
