Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS

Barbara Crone, Michael Aschner, Tanja Schwerdtle, Uwe Karst, Julia Bornhorst

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

cis-Diamminedichloroplatinum(ii) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 μm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose)metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable.

Original languageEnglish (US)
Pages (from-to)1189-1195
Number of pages7
JournalMetallomics
Volume7
Issue number7
DOIs
StatePublished - Jul 1 2015

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Administrative data processing
Inductively coupled plasma mass spectrometry
Caenorhabditis elegans
Laser Therapy
Laser ablation
Cisplatin
Mass Spectrometry
Metabolism
Enzymes
DNA
Pharmacokinetics
Adenosine Diphosphate Ribose
Toxicity
Tumors
Platinum
Cytostatic Agents
Imaging techniques
X-Ray Emission Spectrometry
Poly Adenosine Diphosphate Ribose
DNA Damage

ASJC Scopus subject areas

  • Biomaterials
  • Metals and Alloys
  • Chemistry (miscellaneous)
  • Biochemistry
  • Biophysics

Cite this

Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS. / Crone, Barbara; Aschner, Michael; Schwerdtle, Tanja; Karst, Uwe; Bornhorst, Julia.

In: Metallomics, Vol. 7, No. 7, 01.07.2015, p. 1189-1195.

Research output: Contribution to journalArticle

Crone, B, Aschner, M, Schwerdtle, T, Karst, U & Bornhorst, J 2015, 'Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS', Metallomics, vol. 7, no. 7, pp. 1189-1195. https://doi.org/10.1039/c5mt00096c
Crone, Barbara ; Aschner, Michael ; Schwerdtle, Tanja ; Karst, Uwe ; Bornhorst, Julia. / Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS. In: Metallomics. 2015 ; Vol. 7, No. 7. pp. 1189-1195.
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