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Development of a 2D leukaemia-stroma model for analyses of chemo-toxicity protection using a novel bacterial bioluminescent biosensor

Gynn, Liana; May, Jennifer; Anderson, Elizabeth; Robinson, Gareth

Authors

Liana Gynn

Jennifer May Jennifer2.May@uwe.ac.uk
Senior Lecturer in Biomedical Science

Gareth Robinson Gareth2.Robinson@uwe.ac.uk
Senior Lecturer in Molecular Microbiology



Abstract

This study aimed to develop a 2D leukaemia-stroma model of the bone marrow for analysis of stromal-mediated chemo-protection; known to contribute to chemotherapy resistance. The model must facilitate integration of a bioluminescent biosensor HA1 for chemo sensitivity testing and evaluation of clinical resistance. Leukaemic (HL-60) cells were exposed to conditioned media from stromal (HS-5) cells for 24h prior to treatment with 25 µM cytarabine (ara-C) and/or 5 µM daunorubicin (DA); typical induction therapy for AML. Chemo protection facilitated by HS-5 was determined by cytotoxicity assays and validated against active ara-C metabolite generation using the biosensor. Ara-C induced 40.4% cytotoxicity in HL-60 AML cells, which was reduced to 14% when co-cultured with 25% HS-5 conditioned media (p< 0.01). Preliminary investigations suggest this to be comparable to reduced ara-C metabolite chemo-sensitivity of 23% using co-culture inserts (biosensor assay). This is promising indication for development of a model that will assist in the ongoing evaluation of the biosensor’s physiological and clinical relevance. Future work will further optimise these assays, in addition to genotoxicity assessment to define chemo-protection mechanisms. Combining established interaction and toxicity methodologies with this biosensor assay is a novel way of determining drug-specific chemo-protection in tumour micro-environments.

Journal Article Type Meeting Abstract
Publication Date Nov 1, 2017
Print ISSN 0267-8357
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 32
Issue 6
Pages 619
APA6 Citation Gynn, L., May, J., Anderson, E., & Robinson, G. (2017). Development of a 2D leukaemia-stroma model for analyses of chemo-toxicity protection using a novel bacterial bioluminescent biosensor. Mutagenesis, 32(6), 619. https://doi.org/10.1093/mutage/gex033
DOI https://doi.org/10.1093/mutage/gex033
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