Comparative incorporation of tritium from tritiated water versus tritiated thymidine, uridine or leucine.

D J Mewissen, M Furedi, A Ugarte, J H Rust
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Abstract

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...

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氚化水与氚化胸苷、尿苷或亮氨酸结合的比较。
虽然对氚的放射毒性进行了广泛的研究,但关于其作为一种潜在环境污染物的长期影响的资料相对较少,特别是在小剂量下。本研究的主要目的是比较评估氚化水与DNA、RNA和蛋白质的放射性前体(即氚化胸苷、尿苷和亮氨酸)在C57黑小鼠体内可能的致癌效力。氚主要以氚化水的形式释放到环境中。然而,关于氚是如何从氚化水中定量和定性地加入到细胞成分中的,存在许多不确定性。1965年,我们报道了氚以氚化胸苷的形式在0.3—1.5 muCi/g剂量范围内对新生C57 BL小鼠的致癌作用[Mewissen]。1965]。因此,选择氚化水和氚化前体,试图评估它们各自在氚转移过程中的作用,并将它们可能的后期效应与它们的特定模式或结合位点联系起来。本研究研究了氚化水和各种前体在1或10 muCi水平下的氚掺入。在不同的时间间隔(1、8、15、22和29天),分别给药氚化水、氚化胸苷、尿苷或亮氨酸后,对新生、幼年和成年小鼠的RSA值(即干组织中有机结合氚/氢含量与水中氚/氢含量的比值)进行了估计。目前可用的数据表明,施用氚化水(或前体)会导致有机成分和组织水组分中复杂的时间依赖和年龄依赖的残留活性动态。可以得出一些初步的结论。在一次急性或短暂接触氚化水后,活性值在相对较短的时间内变得非常小。在稳定的平衡状态下,由于长期暴露于氚化的饮用水,RSA值趋于稳定。然而,不同器官之间存在很大的差异,正如单次暴露后各自的RSA值所表明的那样。鉴于这些观察结果,对辐射敏感核的内剂量的现实估计似乎必须考虑到氚从氚化水中随年龄的掺入,以及器官之间的差异。致癌风险通常是根据统一剂量依赖模型估计的。剂量在组织内,特别是在特定部位(如DNA、RNA或蛋白质)的时间和空间微分布的影响,以及在通常较长的潜伏期中剂量吸收的时间序列的相对贡献,迄今很少受到关注。除其他因素外,这些因素可能对内照射致癌至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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