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Dose Response Curve: Conventional Versus Nonmonotonic01:21

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Hormesis predicts low-dose responses better than threshold models.

Edward J Calabrese1, Edward J Stanek, Marc A Nascarella

  • 1Department of Public Health, Environmental Health Sciences Division, University of Massachusetts, Amherst, Massachusetts 01003, USA. edwardc@schoolph.umass.edu

International Journal of Toxicology
|November 28, 2008
PubMed
Summary
This summary is machine-generated.

This study found that chemical responses in yeast often show a hormetic effect, not a threshold effect. This suggests a beneficial low-dose response for many chemicals, impacting toxicology and medicine.

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Area of Science:

  • Toxicology
  • Pharmacology
  • Biochemistry

Background:

  • Dose-response relationships are fundamental in toxicology.
  • The hormesis model describes a biphasic dose response, with low doses stimulating and high doses inhibiting biological processes.
  • The threshold model assumes a safe level below which no adverse effect occurs.

Purpose of the Study:

  • To evaluate concentration-response relationships of chemicals using the National Cancer Institute (NCI) Yeast Anticancer Drug Screen database.
  • To compare the fit of threshold and hormetic dose-response models to experimental data.
  • To investigate the prevalence of hormesis in a large chemical dataset.

Main Methods:

  • Analysis of concentration-response data from 2189 chemicals tested on 13 yeast strains.
  • Inclusion of studies meeting a priori criteria, including concentrations below the Benchmark Dose (BMD).
  • Statistical evaluation of growth responses relative to controls and comparison with predicted values from threshold and hormetic models.

Main Results:

  • Mean growth responses above 100% (105%-111%) were observed across all yeast strains, inconsistent with a strict threshold model.
  • The distribution of responses below the BMD5 was shifted upward, deviating from threshold model expectations.
  • Results strongly support a hormetic dose-response model over a threshold model for the studied chemicals and yeast strains.

Conclusions:

  • The findings provide robust evidence for hormesis in chemical-yeast interactions.
  • Hormesis, characterized by low-dose stimulation, is a significant phenomenon with broad implications for toxicology and drug development.
  • This study reinforces previous evidence for hormesis and its potential relevance in biological systems.