Ver�nderungen der nucleins�ure-synthese durch arsen bei isolierten menschlichen lymphocyten unter anwendung der sedimentations-und ficoll-methode zur zellgewinnung

Petres, J.; Baron, D.; Kunick, I.; Roßner, R.

doi:10.1007/bf00582768

Cited by 9 publications

(1 citation statement)

References 8 publications

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“…The arsenic–thiol reaction can result in the depletion of intracellular glutathione, a major thiol-containing antioxidant, and subsequent oxidative stress. Arsenical has also the ability to disrupt cellular signaling, , and impair mitochondrial function. , Moreover, arsenical is also suggested to alter the expressions of other cellular components, such as lipids and nucleic acids, , and affect various biochemical and physiological processes. Thus, a question is then raised against the current conception: does arsenical toxicity primarily come from binding of arsenic to protein cysteine, i.e., arsenic thiol adhesion?…”

Section: Introductionmentioning

confidence: 99%

Density Functional Theory Calculation May Confirm Arsenic–Thiol Adhesion as the Primary Mechanism of Arsenical Toxicity

Tsai,

Lin

2024

ACS Omega

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Previously, it was believed that methylation was the body's primary method to detoxify inorganic arsenic. However, recent research has shown that the metabolized intermediate known as MMA III is more toxic than arsenite and arsenate, contradicting a previous understanding. Another important question arises: is arsenical toxicity truly caused by arsenic binding to proteins through arsenic thiol adhesion? Based on the toxicity order of the experiment, with MMA III being the most toxic, followed by arsenite, arsenate, DMA V , and MMA V , density functional theory (DFT) calculations can provide a straightforward assessment of this issue. Our practice captures all the transition states associated with a specific imaginary-frequency vibration mode, including proton transfer and simultaneous departure of leaving group. We have obtained the energy barriers for five arsenicals reacting with thiol, alcohol, and amine separately. In addition to energetic favorability, the following are the energy barriers for arsenic's reaction with thiol ranked from low to high: MMA III (25.4 kcal/mol), arsenite (27.7 kcal/mol), arsenate (32.8 kcal/mol), DMA V (36.2 kcal/mol), and MMA V (38.3 kcal/mol). Results show that the toxicity of arsenicals is mainly caused by their reaction with thiol rather than with alcohol or amine, as supported by the trend of decreasing toxicity and increasing energy barriers. Thus, this DFT calculation may confirm the paradigm that arsenic− thiol adhesion is the primary cause of arsenic toxicity in the body.

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Section: Introductionmentioning

confidence: 99%

Density Functional Theory Calculation May Confirm Arsenic–Thiol Adhesion as the Primary Mechanism of Arsenical Toxicity

Tsai,

Lin

2024

ACS Omega

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Synergistical effects of Ficoll and phytohemagglutinin on human lymphocytes

et al. 1978

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Further in vitro studies on the biochemistry of the inhibition of nucleic acid and protein synthesis induced by arsenic

et al. 1975

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Human lymphocytes, stimulated by PHA, and exposed to increasing Na2HAsO4 concentrations, show an identical incorporation rate for 14C thymidine and 14C-TTP into the DNA. 14C uridine is incorporated 3--4 per cent less at an As concentration of 1.0 mug/ml medium, above this however approximately 15 per cent less into the RNA as compared to 14C-UTP. In free pyrimidine bases, the incorporation of labelled triphosphates into the DNA and RNA is significantly reduced above 1 mug and 10 mug Na2HAsO4. Corresponding to its approximately uniform distribution into DNA and RNA, the incorporation rate of 14C-ATP above 10 mug Na2HAsO4/ml culture medium lies between that of 14C-UTP and 14C-TTP. The incorporation of 14C alanine and 14C leucine into cellular protein is not reduced below 10 mug Na2HAsO4/ml. The incorporation rate is 41 per cent at a concentration of 100 mug Na2HAsO4/ml medium. Compared to 14C-UTP, 14C-ATP and 14C-TTP it is increased by the factor of 1.8; 2.5 and 6.8 respectively. The inhibition of enzymes of the dark repair mechanisms and the synthesis of biopolymers together with their altered sequence and the involvement of long-lived messenger RNA serve as an explanation of the observed alterations of the lymphocyte metabolism, caused by arsenic.

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Ver�nderungen der nucleins�ure-synthese durch arsen bei isolierten menschlichen lymphocyten unter anwendung der sedimentations-und ficoll-methode zur zellgewinnung

Cited by 9 publications

References 8 publications

Density Functional Theory Calculation May Confirm Arsenic–Thiol Adhesion as the Primary Mechanism of Arsenical Toxicity

Density Functional Theory Calculation May Confirm Arsenic–Thiol Adhesion as the Primary Mechanism of Arsenical Toxicity

Synergistical effects of Ficoll and phytohemagglutinin on human lymphocytes

Further in vitro studies on the biochemistry of the inhibition of nucleic acid and protein synthesis induced by arsenic

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