PMID- 20736030
OWN - NLM
STAT- MEDLINE
DCOM- 20101025
LR  - 20101004
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 248
IP  - 3
DP  - 2010 Nov 1
TI  - Mechanistic studies of in vitro cytotoxicity of poly(amidoamine) dendrimers in 
      mammalian cells.
PG  - 259-68
LID - 10.1016/j.taap.2010.08.016 [doi]
AB  - Poly(amidoamine) (PAMAM) dendrimer nanoparticles have been demonstrated to elicit 
      a well defined cytotoxicological response from mammalian cell lines, the response 
      increasing systematically with dendrimer generation and number of surface amino 
      groups. In this work, using generation G4, G5, and G6 dendrimers, this systematic 
      response is furthermore demonstrated for the generation of reactive oxygen 
      species, lysosomal activity, and the onset of apoptosis and levels of DNA damage. 
      The results are consistent with a pathway of localisation of PAMAM dendrimers in 
      the mitochondria leading to ROS production causing oxidative stress, apoptosis 
      and DNA damage. ROS production is co-located in the mitochondria, and both 
      generated levels and timescales are systematically generation dependent 
      (G4<G5<G6). Flow cytometry confirms that with increasing dose, the percentage of 
      healthy and early apoptotic cells decreases, whereas the late apoptotic and 
      necrotic cell populations increase. This process is again systematically 
      generation dependent. DNA damage as measured using the TUNEL assay further 
      demonstrates a systematic trend, G4, G5 and G6 showing 4.69%, 25.87% and 89.63% 
      DNA breakage respectively. Increases in lysosomal activity at timescales of ~24h 
      are observed in HaCaT but not SW480 cells upon low concentration PAMAM exposure. 
      Overall, significant differences are observed between the responses of the dermal 
      cell line, HaCaT, and the colon cell line, SW480, and it is suggested that these 
      can be understood in terms of differing intrinsic antioxidant levels.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Mukherjee, Sourav Prasanna
AU  - Mukherjee SP
AD  - Radiation and Environmental Science Centre, Focas Research Institute, Dublin, 
      Institute of Technology, Kevin Street, Dublin 8, Ireland. sourav.mukherjee@dit.ie
FAU - Lyng, Fiona M
AU  - Lyng FM
FAU - Garcia, Amaya
AU  - Garcia A
FAU - Davoren, Maria
AU  - Davoren M
FAU - Byrne, Hugh J
AU  - Byrne HJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100822
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Biocompatible Materials)
RN  - 0 (Cytotoxins)
RN  - 0 (Dendrimers)
RN  - 0 (PAMAM Starburst)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Apoptosis/*drug effects/physiology
MH  - Biocompatible Materials/toxicity
MH  - Cell Line, Transformed
MH  - Cell Line, Tumor
MH  - Cytotoxins/toxicity
MH  - Dendrimers/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Keratinocytes/cytology/*drug effects/metabolism
MH  - Reactive Oxygen Species/metabolism
EDAT- 2010/08/26 06:00
MHDA- 2010/10/26 06:00
CRDT- 2010/08/26 06:00
PHST- 2010/04/01 00:00 [received]
PHST- 2010/07/21 00:00 [revised]
PHST- 2010/08/16 00:00 [accepted]
PHST- 2010/08/26 06:00 [entrez]
PHST- 2010/08/26 06:00 [pubmed]
PHST- 2010/10/26 06:00 [medline]
AID - S0041-008X(10)00301-7 [pii]
AID - 10.1016/j.taap.2010.08.016 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2010 Nov 1;248(3):259-68. doi: 
      10.1016/j.taap.2010.08.016. Epub 2010 Aug 22.