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Dose Response Curve: Conventional Versus Nonmonotonic01:21

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The correlation between a drug's dosage and its impact on a biological system is a cornerstone of pharmacology and toxicology. Conventional dose–response curves, which include graded and quantal relationships, are key to this understanding. Graded dose–response curves depict the spectrum of a biological reaction to different doses within an individual, indicating that as the drug dosage increases, so does the intensity of the response. On the other hand, quantal dose–response relationships...
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Models of Health Promotion and Illness Prevention II01:18

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An R-Based Landscape Validation of a Competing Risk Model
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Published on: September 16, 2022

Changing the Risk Paradigms Can be Good for Our Health: J-Shaped, Linear and Threshold Dose-Response Models.

P F Ricci1, S R Straja, A L Cox

  • 1Holy Names University, Xiamen University, Xiamen, China and University of Massachusetts, Amherst.

Dose-Response : a Publication of International Hormesis Society
|June 29, 2012
PubMed
Summary
This summary is machine-generated.

New models challenge traditional radiation risk assessment, suggesting low-dose benefits are possible. Unlike linear (at low doses)-no-threshold (LNT) and threshold models, these new approaches incorporate hormetic effects for a more realistic risk evaluation.

Keywords:
Biphasic modelscancerlinear-no-threshold (LNT)risk analysistoxic agents

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Expedited Radiation Biodosimetry by Automated Dicentric Chromosome Identification (ADCI) and Dose Estimation

Published on: September 4, 2017

Area of Science:

  • Radiation Biology
  • Toxicology
  • Cancer Research

Background:

  • Traditional models like linear (at low doses)-no-threshold (LNT) and threshold (S-shaped) assume no benefit from low-dose exposures.
  • These models may not fully capture complex biological responses to toxic agents or radiation.
  • A need exists for more flexible models that can account for potential benefits at low exposure levels.

Purpose of the Study:

  • To propose and validate novel dose-response models that allow for, but do not mandate, benefits at low exposure levels.
  • To introduce three hormetic (phasic) models: J-shaped, inverse J-shaped, and min-max.
  • To provide methods for calculating benefits associated with these models, particularly for mutagenic and carcinogenic agents.

Main Methods:

  • Development of three new dose-response models (J-shaped, inverse J-shaped, min-max) incorporating a repair stage for damage.
  • Linking these models to stochastic transition models for cancer.
  • Demonstrating how J-shaped dose-response curves can emerge from smooth increases in cell-level event rates.

Main Results:

  • The proposed models allow for biphasic biological behaviors and potential benefits at low doses.
  • J-shaped and min-max models incorporate an experimentally justified repair stage for toxic and carcinogenic damage.
  • Abrupt transitions in cancer hazard rates can naturally emerge in large cell populations, leading to J-shaped dose-response curves.

Conclusions:

  • The new hormetic models offer a more complete and realistic framework for low-dose risk assessment.
  • These universal models are independent of specific biological details, enhancing their applicability.
  • The findings suggest that low-dose exposures may confer benefits, contrary to LNT and threshold assumptions.