Related Experiment Video
Updated: Jan 28, 2026
08:21
Determination of Inorganic Arsenic in a Wide Range of Food Matrices using Hydride Generation - Atomic Absorption Spectrometry.
Published on: September 1, 2017
16.0K
Functional Profiling Identifies Determinants of Arsenic Trioxide Cellular Toxicity
Amin Sobh1,2, Alex Loguinov1, Gulce Naz Yazici1,3
1Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.
Summary
Arsenic trioxide (AsIII) shows promise for chronic myeloid leukemia (CML) therapy. This study identified key genes that modulate AsIII toxicity, revealing potential targets to enhance its effectiveness in CML treatment.
Area of Science:
- Biochemistry
- Genetics
- Oncology
Background:
- Arsenic trioxide (AsIII) is an effective chemotherapy for acute promyelocytic leukemia (APL).
- AsIII is being explored for other cancers like chronic myeloid leukemia (CML), especially in combination therapies.
- Understanding AsIII toxicity modulation is crucial for optimizing its therapeutic use.
Purpose of the Study:
- To identify genes and cellular pathways that modulate arsenic trioxide (AsIII) toxicity in chronic myeloid leukemia (CML) cells.
- To uncover potential targets for enhancing AsIII efficacy in CML therapy.
Main Methods:
- Genome-wide CRISPR-based screening in K562 human CML cells.
- Identification of genes influencing sensitivity or resistance to AsIII.
Main Results:
- Disruption of KEAP1, TXNDC17, AQP3, ZNT1, and MTF1 increased AsIII tolerance.
- Loss of ABCC1 enhanced AsIII sensitivity.
- Disruption of selenocysteine metabolism genes (EEFSEC, SECISBP2, SEPHS2, SEPSECS, PSTK) conferred AsIII resistance.
- A model suggesting selenium-AsIII interaction influencing intracellular AsIII levels and toxicity was proposed.
Conclusions:
- Multiple cellular components and processes modulate AsIII toxicity in CML.
- Targeting these pathways concurrently with AsIII could potentiate its efficacy in CML treatment.
- This research provides novel insights into AsIII's mechanism of action and therapeutic potential in CML.
Related Concept Videos
01:26Toxic Reactions: Overview
1.9K
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,...
1.9K
02:24Ribosome Profiling
4.2K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
4.2K
00:57Cellular Differentiation
5.3K
How does a complex organism such as a human develop from a single cell? It all starts from a single fertilized egg which gives rise to a vast array of cell types, such as nerve cells, muscle cells, and epithelial cells that characterize the adult? Throughout development and adulthood, cellular differentiation leads cells to assume their final morphology and physiology. Differentiation is the process by which unspecialized cells become specialized to carry out distinct functions.
A zygote is a...
A zygote is a...
5.3K
01:18Cellular Respiration
1.9K
Cellular respiration is a crucial metabolic process through which cells obtain energy from organic substances, mainly glucose, to produce adenosine triphosphate (ATP). This process includes the oxidation of substrates and the transfer of electrons to a separate electron acceptor, facilitating ATP synthesis through a sequence of biochemical reactions.Glycolysis: The Initial StepGlycolysis is the first stage of cellular respiration, occurring in the cytoplasm of both prokaryotic and eukaryotic...
1.9K
02:53Determining Order of Reaction
61.9K
Rate laws describe the relationship between the rate of a chemical reaction and the concentration of its reactants. In a rate law, the rate constant k and the reaction orders are determined experimentally by observing how the rate of reaction changes as the concentrations of the reactants are changed. A common experimental approach to the determination of rate laws is the method of initial rates. This method involves measuring reaction rates for multiple experimental trials carried out using...
61.9K
01:51Determination
20.9K
During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
20.9K