Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-8-2
pubmed:abstractText
Poly(2-(dimethylamino ethyl)methacrylate) (pDMAEMA) is a cationic polymer with potential as an antimicrobial agent and as a non-viral gene delivery vector. The aim was to further elucidate the cytotoxicity of a selected pDMAEMA low molecular weight (MW) polymer against human U937 monocytes and Caco-2 intestinal epithelial cells using a novel multi-parameter high content analysis (HCA) assay and to investigate histological effects on isolated rat intestinal mucosae. Seven parameters of cytotoxicity were measured: nuclear intensity (NI), nuclear area (NA), intracellular calcium ([Ca(2+)]i), mitochondrial membrane potential (MMP), plasma membrane permeability (PMP), cell number (CN) and phospholipidosis. Histological effects of pDMAEMA on excised rat ileal and colonic mucosae were investigated in Ussing chambers. Following 24-72 h exposure, 25-50 microg/ml pDMAEMA induced necrosis in U937 cells, while 100-250 microg/ml induced apoptosis in Caco-2. pDMAEMA increased NA and NI and decreased [Ca(2+)]i, PMP, MMP and CN in U937 cells. In Caco-2, it increased NI and [Ca(2+)]i, but decreased NA, PMP, MMP and CN. Phospholipidosis was not observed in either cell line. pDMAEMA (10 mg/ml) did not induce any histological damage on rat colonic tissue and only mild damage to ileal tissue following exposure for 60 min. In conclusion, HCA reveals that pDMAEMA induces cytotoxicity in different ways on different cell types at different concentrations. HCA has potential for high throughput toxicity screening in drug formulation programmes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1873-4995
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
146
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
84-92
pubmed:meshHeading
pubmed-meshheading:20457190-Animals, pubmed-meshheading:20457190-Apoptosis, pubmed-meshheading:20457190-Biological Assay, pubmed-meshheading:20457190-Caco-2 Cells, pubmed-meshheading:20457190-Calcium, pubmed-meshheading:20457190-Cell Count, pubmed-meshheading:20457190-Cell Membrane Permeability, pubmed-meshheading:20457190-Cell Nucleus, pubmed-meshheading:20457190-Cell Survival, pubmed-meshheading:20457190-Dose-Response Relationship, Drug, pubmed-meshheading:20457190-Humans, pubmed-meshheading:20457190-Ileum, pubmed-meshheading:20457190-Intestinal Mucosa, pubmed-meshheading:20457190-Membrane Potential, Mitochondrial, pubmed-meshheading:20457190-Methacrylates, pubmed-meshheading:20457190-Molecular Weight, pubmed-meshheading:20457190-Monocytes, pubmed-meshheading:20457190-Nylons, pubmed-meshheading:20457190-Rats
pubmed:year
2010
pubmed:articleTitle
High content analysis of cytotoxic effects of pDMAEMA on human intestinal epithelial and monocyte cultures.
pubmed:affiliation
UCD School of Veterinary Medicine, University College Dublin, Dublin 4, Ireland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't