Trosko J E, Chang C C
Basic Life Sci. 1985;33:261-84. doi: 10.1007/978-1-4684-4970-9_15.
The assessment of risk from low-level exposure to radiation and chemicals is hindered by the basic lack of scientific understanding of the complex nature of the multiple levels of protective or synergistic interactions. Radiation and chemicals have the potential of inducing mutations, cell death and altered gene expression. The biological consequences of each of these effects is again complex, since many factors can enhance or mask the effect of a single mutation, cytotoxic or gene modulatory change. Carcinogenesis, representing but one chronic disease state, is a multi-step process, involving the clonal expansion of a single altered cell (that is, the initiation event). Radiation and chemicals appear to contribute to the initiation process by their ability to induce viable mutations. Insufficient theoretical and empirical knowledge precludes a determination of whether mutagenesis and, hence, initiation exhibit a threshold phenomenon. Because of a variety of redundancy mechanisms on the genetic and cellular levels, the physiological impact of a single dysfunctional cell is felt only after it is amplified to a large number (the promotion phase of carcinogenesis). Radiation and chemical-induced cytotoxicity, as well as noncytotoxic chemical induction of mitogenesis, can induce surviving single dysfunctional stem cells to multiply. If during this multiplication of dysfunctional cells, the initiated cells are further exposed chronically to low levels of mutagens, there is an enhanced probability of additional genetic changes. The accumulation of foci of dysfunctional cells can occur in any stem cell population of any tissue. As with mutagens, the existence of threshold levels for promoting conditions and chemicals is still not yet scientifically validated. However, specific examples of the actions of a few promoters does seem to be consistent with that idea. The concepts of initiation and promotion imply the existence of anti-initiation and antipromotion conditions. Together with genetic factors, the complex and unpredictable interactions of radiation and chemicals as initiators, anti-initiators, promoters and antipromoters, defy prospects of an easy means to predict the consequences of exposure to chronic low levels of radiation and chemicals.
对低水平辐射和化学物质暴露风险的评估受到阻碍，因为从根本上来说，我们对多重保护或协同相互作用的复杂本质缺乏科学认识。辐射和化学物质有可能诱发突变、导致细胞死亡并改变基因表达。而这些影响中的每一种所产生的生物学后果同样复杂，因为许多因素能够增强或掩盖单个突变、细胞毒性或基因调节变化的影响。致癌作用只是一种慢性病状态，是一个多步骤过程，涉及单个改变细胞的克隆扩增（即引发事件）。辐射和化学物质似乎通过其诱导存活突变的能力对引发过程有所影响。理论和实证知识的不足使得我们无法确定诱变作用以及由此产生的引发过程是否存在阈值现象。由于遗传和细胞层面存在多种冗余机制，单个功能失调细胞的生理影响只有在其扩增到大量细胞后才会显现出来（致癌作用的促进阶段）。辐射和化学物质诱导的细胞毒性，以及化学物质对有丝分裂的非细胞毒性诱导，都能够促使存活的单个功能失调干细胞增殖。如果在这些功能失调细胞增殖过程中，引发细胞长期进一步暴露于低水平诱变剂中，那么发生额外基因变化的可能性就会增加。功能失调细胞聚集点可能出现在任何组织的任何干细胞群体中。与诱变剂一样，促进条件和化学物质的阈值水平是否存在仍未得到科学验证。然而，少数促进剂作用的具体例子似乎与这一观点相符。引发和促进的概念意味着存在抗引发和抗促进条件。与遗传因素一起，辐射和化学物质作为引发剂、抗引发剂、促进剂和抗促进剂的复杂且不可预测的相互作用，使得难以找到一种简便方法来预测长期低水平辐射和化学物质暴露的后果。
