title: Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS.
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.
authors.affiliation: University of Münster, Institute of Inorganic and Analytical Chemistry, Corrensstraße 30, 48149 Münster, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Crone
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.forename: Tanja
authors.initials: T
authors.lastname: Schwerdtle
authors.forename: Uwe
authors.initials: U
authors.lastname: Karst
authors.forename: Julia
authors.initials: J
authors.lastname: Bornhorst
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000633:toxicity*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology*; D002945:Cisplatin / Q000493:pharmacokinetics* / Q000633:toxicity*; D013058:Mass Spectrometry / Q000379:methods*; D012098:Reproduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin