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Related Concept Videos

Dose Response Curve: Conventional Versus Nonmonotonic01:21

Dose Response Curve: Conventional Versus Nonmonotonic

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...
Dose-Response Relationship: Overview01:03

Dose-Response Relationship: Overview

Agonists can bind with and activate receptors, resulting in the formation of drug-receptor complexes. Once formed, these complexes catalyze many biochemical processes at the cellular level and subsequently induce a pharmacologic response. The degree of response is directly proportional to the fraction of activated receptors, which in turn, depends on the concentration of the drug at the receptor site as well as the sensitivity of the receptor. An increase in the administered dose contributes to...
Dose-Response Relationship: Potency and Efficacy01:22

Dose-Response Relationship: Potency and Efficacy

The potency of a drug is the measure of its ability to produce a biological response and can be compared by looking at the half-maximum effective concentration or EC50 values of different drugs. A lower EC50 value indicates higher potency of the drug. In the dose–response curve of two antihypertensive drugs, candesartan and irbesartan, a significant difference is observed in their EC50 values. A lower EC50 value for candesartan indicates that it is more potent than irbesartan, as it produces...
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
Agonism and Antagonism: Quantification01:14

Agonism and Antagonism: Quantification

When drugs are administered, they can elicit either an agonist or antagonist effect on the body. Agonism occurs when a drug activates a specific receptor, triggering a biological response. On the other hand, antagonism happens when a drug binds to the same receptors but blocks their activation, thereby preventing a biological response.
To quantify these effects, researchers use a dose-response curve, which provides valuable information about the potency and efficacy of a drug. Potency refers to...
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...

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Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
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Quantification of hormesis in anticancer-agent dose-responses.

Marc A Nascarella1, Edward J Stanek, George R Hoffmann

  • 1Department of Public Health, Environmental Health Sciences Division, University of Massachusetts-Amherst, Amherst, MA, USA. mnascarella@gradientcorp.com

Dose-Response : a Publication of International Hormesis Society
|June 23, 2009
PubMed
Summary

This study analyzed 2,189 anticancer agents in yeast, finding that over half exhibit hormetic dose responses. These findings characterize the quantitative features of hormesis for potential drug development.

Keywords:
anti-tumorbiphasichormesislow-dosethresholdyeast

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Area of Science:

  • Pharmacology and Toxicology
  • Yeast Genetics and Molecular Biology
  • Chemical Biology

Background:

  • Previous research indicated that dose responses below toxic thresholds are often stimulatory.
  • Hormetic dose-response models better explain these stimulatory effects than threshold models.

Purpose of the Study:

  • To quantitatively characterize hormetic concentration-responses for 2,189 candidate anticancer agents in 13 yeast strains.
  • To determine the prevalence of hormesis across diverse chemical classes.

Main Methods:

  • Analysis of quantitative features of 4,548 hormetic concentration-responses using established criteria.
  • Evaluation of 2,189 diverse chemical compounds, including mustards, alkylating agents, and antimetabolites.
  • Testing across 13 strains of Saccharomyces cerevisiae.

Main Results:

  • Over half (52.5%) of the evaluated chemicals displayed hormetic dose responses in at least one yeast strain.
  • Key quantitative features identified include: a 5-fold mean stimulation range, 27% mean maximum stimulation, and a 3.7-fold mean range to the toxic threshold.
  • 24 agents demonstrated hormesis across all 13 yeast strains.

Conclusions:

  • Hormesis is a common dose-response phenomenon among candidate anticancer agents in yeast.
  • The characterized quantitative features provide a basis for understanding and utilizing hormesis in drug discovery.
  • Findings contribute to the broader understanding of hormetic dose-response relationships in chemical biology.