Evidence map›Paper›PMID 12773768›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2003

Thimerosal induces DNA breaks, caspase-3 activation, membrane damage, and cell death in cultured human neurons and fibroblasts.

David S Baskin, Hop Ngo, Vladimir V Didenko

Open access · bronzeAbstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 115 citations in OpenAlex.

  1. Article
  2. Review
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  7. N-3 vs. n-6 fatty acids differentially influence calcium signalling and adhesion of inflammatory activated monocytes: impact of lipid rafts.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2016
    Article
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  15. Review
  16. Article
  17. Infants' exposure to aluminum from vaccines and breast milk during the first 6 months.Journal of exposure science & environmental epidemiology · 2010
    Article
  18. Thimerosal-containing vaccines and autism: a review of recent epidemiologic studies.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2010
    Article
  19. Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2009
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

David S BaskinDepartment of Neurosurgery, Baylor College of Medicine, 6560 Fannin Suite 944, Houston, Texas 77030, USA. dbaskin@tmh.tmc.edu
Hop Ngo
Vladimir V Didenko
Baylor College of Medicine · US

Funding

Improved Diagnostic MRI around Metallic ImplantsR01AR078912 · NIAMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Brian Andrew Hargreaves, Krishna Shrinivas Nayak · 2022 to 2026
$2.4M
IN SITU LIGATION FOR DETECTION OF SPECIFIC DNA DAMAGER01CA078912 · NCI · BAYLOR COLLEGE OF MEDICINE · PI BASKIN, DAVID S. · 1998 to 2001
$138k
NCI NIH HHS R01 CA078912-02NCI NIH HHS R01 CA78912-01NIAMS NIH HHS R01 AR078912
6 · The paper itself

Abstract

Thimerosal is an organic mercurial compound used as a preservative in biomedical preparations. Little is known about the reactions of human neuronal and skin cells to its micro- and nanomolar concentrations, which can occur after using thimerosal-containing products. A useful combination of fluorescent techniques for the assessment of thimerosal toxicity is introduced. Short-term thimerosal toxicity was investigated in cultured human cerebral cortical neurons and in normal human fibroblasts. Cells were incubated with 125-nM to 250-microM concentrations of thimerosal for 45 min to 24 h. A 4', 6-diamidino-2-phenylindole dihydrochloride (DAPI) dye exclusion test was used to identify nonviable cells and terminal transferase-based nick-end labeling (TUNEL) to label DNA damage. Detection of active caspase-3 was performed in live cell cultures using a cell-permeable fluorescent caspase inhibitor. The morphology of fluorescently labeled nuclei was analyzed. After 6 h of incubation, the thimerosal toxicity was observed at 2 microM based on the manual detection of the fluorescent attached cells and at a 1-microM level with the more sensitive GENios Plus Multi-Detection Microplate Reader with Enhanced Fluorescence. The lower limit did not change after 24 h of incubation. Cortical neurons demonstrated higher sensitivity to thimerosal compared to fibroblasts. The first sign of toxicity was an increase in membrane permeability to DAPI after 2 h of incubation with 250 microM thimerosal. A 6-h incubation resulted in failure to exclude DAPI, generation of DNA breaks, caspase-3 activation, and development of morphological signs of apoptosis. We demonstrate that thimerosal in micromolar concentrations rapidly induce membrane and DNA damage and initiate caspase-3-dependent apoptosis in human neurons and fibroblasts. We conclude that a proposed combination of fluorescent techniques can be useful in analyzing the toxicity of thimerosal.

Indexed as

ApoptosisCaspase 3Caspase InhibitorsCaspasesCell MembraneCell NucleusCells, CulturedCell SurvivalCerebral CortexDNA DamageDose-Response Relationship, DrugFibroblastsHumansInfant, NewbornIn Situ Nick-End LabelingMaleCASP3 protein, humanCaspase 3Caspase InhibitorsCaspasesPreservatives, PharmaceuticalThimerosal

Identifiers

PMID12773768
PMCPMC1892749
OpenAlexW2154186851

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.