Calabrese Edward J
Department of Public Health, Environmental Health Sciences, University of Massachusetts, Morrill I, N344 Amherst, MA 01003, USA.
Biogerontology. 2006 Apr;7(2):119-22. doi: 10.1007/s10522-006-0005-z.
Recent detailed evaluations of the pharmacological, toxicological, and biogerontological literature indicate that the hormetic dose-response is quite common and highly generalizable by biological model, endpoint, and chemical class. Head-to-head comparisons of the hormetic model with the traditional threshold model have revealed the hormetic model to occur with considerably greater frequency in the biomedical literature. Despite these developments, the history of both pharmacology and toxicology reflects a strong acceptance and centralizing of the threshold model concept while profoundly marginalizing of the hormetic dose-response. This commentary will address why the biomedical community especially those in the areas of pharmacology and toxicology made an incorrect judgment that the most fundamental nature of the dose-response was threshold rather than hormetic and why this conclusion has continued to dominate these fields and their numerous applications despite convincing evidence to the contrary. These findings have particular relevance to the area of biogerontology since this discipline often resides at the pharmacological-toxicological interface.
近期对药理学、毒理学和生物老年医学文献的详细评估表明，毒物兴奋效应剂量反应相当常见，并且在生物学模型、终点指标和化学类别方面具有高度的普遍性。毒物兴奋效应模型与传统阈值模型的直接比较显示，在生物医学文献中，毒物兴奋效应模型出现的频率要高得多。尽管有这些进展，但药理学和毒理学的历史都反映出对阈值模型概念的强烈接受和集中化，而毒物兴奋效应剂量反应则被严重边缘化。本评论将探讨为什么生物医学领域，尤其是药理学和毒理学领域的人做出了错误的判断，即剂量反应的最基本性质是阈值而非毒物兴奋效应，以及为什么尽管有相反的确凿证据，这一结论仍继续主导着这些领域及其众多应用。这些发现与生物老年医学领域特别相关，因为该学科通常处于药理学与毒理学的交叉点。
