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Title: Stem cell proliferation patterns as an alternative for in vivo prediction and discrimination of carcinogenic compounds
Authors: Stevens, An-Sofie 
Willems, Maxime
Plusquin, Michelle 
Ploem, Jan-Pieter 
Winckelmans, Ellen 
Artois, Tom 
Smeets, Karen 
Issue Date: 2017
Source: SCIENTIFIC REPORTS, 7, p. 1-11 (Art N° 45616)
Abstract: One of the major challenges in the development of alternative carcinogenicity assays is the prediction of non-genotoxic carcinogens. The variety of non-genotoxic cancer pathways complicates the search for reliable parameters expressing their carcinogenicity. As non-genotoxic and genotoxic carcinogens have different cancer risks, the objective of this study was to develop a concept for an in vivo test, based on flatworm stem cell dynamics, to detect and classify carcinogenic compounds. Our methodology entails an exposure to carcinogenic compounds during the animal's regeneration process, which revealed differences in proliferative responses between non-genotoxic and genotoxic carcinogens during the initial stages of the regeneration process. A proof of concept was obtained after an extensive study of proliferation dynamics of a genotoxic and a non-genotoxic compound. A pilot validation with a limited set of compounds showed that the proposed concept not only enabled a simple prediction of genotoxic and non-genotoxic carcinogens, but also had the power to discriminate between both. We further optimized this discrimination by combining stem cell proliferation responses with a phenotypic screening and by using specific knockdowns. In the future, more compounds will be tested to further validate and prove this concept.
Notes: [Stevens, An-Sofie; Ploem, Jan-Pieter; Artois, Tom; Smeets, Karen] Hasselt Univ, Ctr Environm Sci, Zool Biodivers & Toxicol, Agoralaan,Bldg D, BE-3590 Diepenbeek, Belgium. [Willems, Maxime] Univ Ghent, Fac Pharmaceut Sci, Lab Pharmaceut Technol, Ottergemsesteenweg 460, Ghent, Belgium. [Willems, Maxime] Univ Ghent, Lab Environm Toxicol & Aquat Ecol, Jozef Plateaustr 22, BE-9000 Ghent, Belgium. [Plusquin, Michelle] Imperial Coll London, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, St Marys Campus,Norfolk Pl W2 IPG, London, England. [Plusquin, Michelle; Winckelmans, Ellen] Hasselt Univ, Ctr Environm Sci, Environmental Biol, Agoralaan,Bldg D, BE-3590 Diepenbeek, Belgium.
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ISSN: 2045-2322
e-ISSN: 2045-2322
DOI: 10.1038/srep45616
ISI #: 000400467600001
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Category: A1
Type: Journal Contribution
Validations: ecoom 2018
Appears in Collections:Research publications

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