Related Experiment Video
Updated: Jun 19, 2026
17:28
Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Chemical target and pathway toxicity mechanisms defined in primary human cell systems
Ellen L Berg1, Jian Yang, Jennifer Melrose
1BioSeek, Inc., 310 Utah #100, South San Francisco, CA 94080, USA. eberg@bioseekinc.com
Journal of Pharmacological and Toxicological Methods
|November 3, 2009
Summary
BioMAP systems, using primary human cells, effectively identify and classify chemical toxicity mechanisms. This cost-effective approach aids in predicting health effects from drug or chemical exposure by analyzing compound activity profiles.
Area of Science:
- Toxicology
- Cell-based assays
- Drug discovery
Background:
- Predicting chemical health effects is complex due to human biology.
- Need for predictive, cost-effective testing for broad mechanism detection.
Purpose of the Study:
- Evaluate BioMAP systems for characterizing chemical toxicity mechanisms.
- Assess performance in discriminating compounds based on mechanisms of action.
Main Methods:
- Utilized BioMAP systems with primary human cells.
- Tested compounds in 8 assays for respiratory, skin, immune, and vascular sites.
- Compared activity profiles in reduced sample format to reference databases.
Main Results:
- Successfully detected and distinguished compounds by mechanism of action.
- BioMAP assay panel size and concentration influenced discrimination.
- Classified compounds modulating NFkappaB, microtubule, and mitochondrial pathways.
Conclusions:
- BioMAP systems can classify compounds into target and pathway mechanisms.
- Identified specific mitochondrial inhibitors misclassified with endoplasmic reticulum stress inducers.
- Method shows utility for classifying novel agents by toxicity pathway effects.
More Related Videos
Related Concept Videos
01:26Toxic Reactions: Overview
When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
01:25Bioactivation and Tissue Toxicity
Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
01:23Toxicity Testing in Animals
Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...
01:24Drug 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...
01:21Toxicokinetics: Overview
Studies that assess how a drug is absorbed, distributed, metabolized, and excreted (ADME) at toxic doses are termed toxicokinetics. Understanding toxicokinetics helps predict adverse drug reactions (ADRs) and manage toxicity in humans.Toxicokinetics differs from pharmacokinetics mainly in the dose levels studied, with toxicokinetics focusing on higher toxic doses. The kinetics at these levels can be non-linear due to altered physiological processes. Toxicodynamics examines the relationship...
01:00Drug Toxicity: Overview
Drug toxicity quantifies the harm a compound causes to an organism, varying by dose and potentially impacting whole systems or specific organs like the liver. Toxic reactions may arise from venomous insect or spider bites, with effects ranging from mild symptoms to severe outcomes such as brain damage or death. Common forms of acute poisoning include ethanol intoxication and overdose of pain or fever medications, with substances like GHB and heroin being particularly lethal at doses close to...