Pathology Department, Stony Brook University, Stony Brook, NY 11974, USA.
Int J Environ Res Public Health. 2013 Jul 2;10(7):2735-40. doi: 10.3390/ijerph10072735.
We thank Dr. Baverstock [1] for his interest in reading our article and his time in writing his comments for our work [2]. We, however, respectfully disagree with his statement that we made "two category errors" associated with the assessment of the occurrence of "genomic instability" by determining the frequencies of delayed- or late-occurring chromosomal damage. Our disagreement is based upon the well-known fact that radiation-induced genomic instability (or delayed/late-occurring damage) can be manifested in many ways. These include late-occurring chromosomal damage, or mutations, or gene expression, or gene amplifications, or transformation, or microsatellite instability, or cell killing [3-9]. Such phenomena have been detected many cell generations after irradiation. We agree that genomic instability may well be the consequence of epigenetic changes. Another mechanism mentioned by Dr. Bavertock as being probably unlikely is the reversibility of damage. This potential may not be discarded off-hand, as Dr. Baverstock prefers to do. There is much reproducible evidence of adaptive protection that depending on absorbed dose precisely may reverse early damage, and damage appearing late may be due to some form of residual damage letting the cell become genetically unstable. In other words, the argument by Dr. Baverstock regarding upward or downward causation appears to be rather speculative and far from being settled.
我们感谢 Baverstock 博士对阅读我们的文章并抽出时间为我们的工作撰写评论的关注[2]。然而,我们不同意他的观点,即我们在评估“基因组不稳定性”的发生时犯了“两个范畴错误”,其方法是确定延迟或晚期染色体损伤的频率。我们的分歧是基于这样一个众所周知的事实,即辐射诱导的基因组不稳定性(或延迟/晚期损伤)可以通过多种方式表现出来。这些包括晚期染色体损伤、突变、基因表达、基因扩增、转化、微卫星不稳定性或细胞杀伤[3-9]。这些现象在照射后许多代细胞中都有检测到。我们同意基因组不稳定性可能是表观遗传变化的结果。Baverstock 博士提到的另一种可能不太可能的机制是损伤的可逆性。这种可能性不应被轻易排除,因为 Baverstock 博士更倾向于这样做。有许多可重复的适应性保护证据表明,吸收剂量可能会精确地逆转早期损伤,而晚期出现的损伤可能是由于某种形式的残留损伤导致细胞遗传不稳定。换句话说,Baverstock 博士关于因果关系的论点似乎相当推测,远未得到解决。