Mewissen D J, Furedi M, Ugarte A, Rust J H
Curr Top Radiat Res Q. 1978 Jan;12(1-4):225-54.
Whereas the radiotoxicity of tritium has been extensively studied, comparatively little information exists on its long-term effects as a potential environmental pollutant, particularly at small dosage. This investigation was primarily aimed at assessing comparatively a possible carcinogenic potency of tritiated water versus radioactive precursors of DNA, RNA and proteins, namely tritiated thymidine, uridine and leucine in C57 Black mice. Tritium is largely released in the environment in the form of tritiated water. There are many uncertainties, however, as to how tritium is incorporated from tritiated water into cell constituents quantitively and qualitatively. In 1965, we reported on the carcinogenic effect of tritium in the form of tritiated thymidine on newborn C57 BL mice in the dose range of 0.3--1.5 muCi/g [Mewissen. 1965]. Hence the selection of tritiated water, and of tritiated precursors, in an attempt to evaluate their respective role in the tritium transfer process and to correlate their possible late effects with their specific patterns or sites of incorporation. This study deals with tritium incorporation from tritiated water and various precursors at the 1 or 10 muCi level. RSA values, i.e., the ratio of organically bound tritium per hydrogen content of dry tissue over aqueous tritium per hydrogen content of water, were estimated for newborn, juvenile and adult mice, at various time intervals (1, 8, 15, 22 and 29 days) following single administration of tritiated water, tritiated thymidine, uridine or leucine. The data available at this time show that administration of tritiated water (or precursors) result in a complex time dependent and age dependent residual activity dynamics both in the organic component and in the aqueous fraction of tissue. A few preliminary conclusions can be made. Following a single acute or brief exposure to tritiated water, values of activity become exceedingly small after a relatively short time period. In a steady state equilibrium, resulting from chronic exposure to tritiated drinking water, RSA values tend to stabilize. However, wide variations between various organs are to be expected, as suggested by their respective RSA values following a single exposure. In view of these observations, it would seem that a realistic estimate of the internal dose to the radiosensitive nucleus must take into consideration the age dependent incorporation of tritium from tritiated water, as well as the variation between organs. The carcinogenic risk has often been estimated from a uniform dose dependency model. The influence of time and space microdistribution of dose within tissues and more particularly at specific sites (such as DNA, RNA or protein) has received, as yet, little attention, as well as the relative contributions of the time sequence of dose absorption during the usually long latency period. Such factors, among others, may be critical in carcinogenesis from internal irradiation...
尽管氚的辐射毒性已得到广泛研究,但关于其作为潜在环境污染物的长期影响,特别是小剂量情况下的信息相对较少。本研究主要旨在比较氚水与DNA、RNA和蛋白质的放射性前体(即氚化胸腺嘧啶核苷、尿苷和亮氨酸)在C57黑小鼠体内的潜在致癌能力。氚主要以氚水的形式释放到环境中。然而,关于氚如何从氚水定量和定性地掺入细胞成分,存在许多不确定性。1965年,我们报道了氚化胸腺嘧啶核苷形式的氚在0.3 - 1.5微居里/克剂量范围内对新生C57 BL小鼠的致癌作用[Mewissen. 1965]。因此选择氚水和氚化前体,试图评估它们在氚转移过程中的各自作用,并将它们可能的后期影响与其特定的掺入模式或部位相关联。本研究涉及在1或10微居里水平下,氚从氚水和各种前体的掺入情况。在新生、幼年和成年小鼠单次给予氚水、氚化胸腺嘧啶核苷、尿苷或亮氨酸后的不同时间间隔(1、8、15、22和29天),估计了RSA值,即干组织中有机结合氚的氢含量与水中氚的氢含量之比。目前可得的数据表明,给予氚水(或前体)会导致组织的有机成分和水相部分中残留活性呈现复杂的时间依赖性和年龄依赖性动态变化。可以得出一些初步结论。单次急性或短期接触氚水后,活性值在相对较短的时间内变得极小。在长期接触氚化饮用水导致的稳态平衡中,RSA值趋于稳定。然而,正如单次接触后各器官各自的RSA值所示,不同器官之间预计会有很大差异。鉴于这些观察结果,对辐射敏感细胞核的内照射剂量进行实际估计时,似乎必须考虑氚从氚水的年龄依赖性掺入以及器官之间的差异。致癌风险通常是根据统一的剂量依赖性模型估计的。组织内剂量的时间和空间微分布,特别是在特定部位(如DNA、RNA或蛋白质)的微分布,以及在通常较长的潜伏期内剂量吸收的时间顺序的相对贡献,迄今为止很少受到关注。诸如此类因素可能在内部照射致癌过程中起关键作用……