Environmental and Occupational Health Sciences Institute, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
Chem Biol Interact. 2010 Mar 19;184(1-2):273-8. doi: 10.1016/j.cbi.2010.01.031. Epub 2010 Jan 28.
The concept of the vanishing zero, which was first discussed 50 years ago in relation to pesticide residues in foods and food crops, focused on the unintended regulatory consequences created by ever-increasing sensitivity and selectivity of analytical methods, in conjunction with the ambiguous wording of legislation meant to protect public health. In the interim, the ability to detect xenobiotics in most substrates has increased from tens of parts per million to parts per trillion or less, challenging our ability to interpret the biological significance of exposures at the lowest detectable levels. As a result the focus of risk assessment, especially for potential carcinogens, has shifted from defining an acceptable level, to extrapolating from the best available analytical results. Analysis of gene expression profiles in exposed target cells using genomic technologies can identify biological pathways induced or repressed by the exposure as a function of dose and time. This treatise explores how toxicogenomic responses at low doses may inform risk assessment and risk management by defining thresholds for cellular responses linked to modes or mechanisms of toxicity at the molecular level.
“消失的零值”概念最早是在 50 年前提出的，当时是为了应对食品和农作物中的农药残留问题，主要关注的是分析方法的灵敏度和选择性不断提高，以及旨在保护公众健康的法规措辞模糊，由此带来的意料之外的监管后果。在此期间，大多数基质中检测外来化合物的能力已经从百万分之几十提高到了万亿分之几甚至更低，这使得我们很难解释在最低可检测水平下暴露的生物学意义。因此，风险评估的重点，特别是对潜在致癌物的风险评估，已经从确定可接受水平，转变为从最佳可用分析结果外推。利用基因组技术分析暴露靶细胞中的基因表达谱，可以根据剂量和时间，确定暴露诱导或抑制的生物学途径。本文探讨了在低剂量下的毒代基因组反应如何通过定义与分子水平毒性模式或机制相关的细胞反应阈值，为风险评估和风险管理提供信息。
