Related Experiment Video
Updated: May 17, 2026
07:08
The Lambda Select cII Mutation Detection System
Published on: April 26, 2018
Mutagenicity, carcinogenicity, and other end points.
Romualdo Benigni1, Chiara Laura Battistelli, Cecilia Bossa
1Environment and Health Department, Istitituto Superiore di Sanita', Rome, Italy. romualdo.benigni@iss.it
Methods in Molecular Biology (Clifton, N.J.)
|October 23, 2012
Summary
Structure-activity relationship (SAR) science has advanced, offering qualitative and quantitative models to predict chemical toxicity. Recent tools like databases and expert systems enhance SAR analysis for chemists, toxicologists, and regulators.
Area of Science:
- Computational chemistry
- Toxicology
- cheminformatics
Background:
- Structure-activity relationship (SAR) science has progressed significantly.
- Traditional qualitative (structural alerts) and quantitative (QSAR) models predict chemical biological activity and toxicity.
- Recent advancements provide crucial support and corollary concepts to SAR methods.
Purpose of the Study:
- To provide an overview of traditional SAR approaches.
- To detail recent, publicly available support tools for SAR analysis.
- To highlight the importance of these tools for computational chemists, toxicologists, and regulators.
Main Methods:
- Review of traditional structure-activity relationship models.
- Presentation of recent support tools, including chemical relational databases, expert systems, and software for chemical information manipulation.
- Focus on freely available public domain resources.
Main Results:
- Development of both coarse-grain qualitative and fine-tuned quantitative structure-activity relationship models.
- Emergence of new approaches and concepts supporting SAR methods.
- Expansion of SAR work's reach through advanced tools.
Conclusions:
- Structure-activity relationship science is a powerful tool for understanding chemical biological activity.
- Recent computational and data management tools have become indispensable for SAR analysis.
- Publicly available resources significantly enhance the capabilities of chemists, toxicologists, and regulators in chemical assessment.
Related Concept Videos
01:25Mutagenicity 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...
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...
01:26Toxic 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,...
01:24Drug 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...
01:30Spontaneous and Induced Mutations
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).