PMID- 26719368
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20181113
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 150
IP  - 1
DP  - 2016 Mar
TI  - Screening for Chemical Toxicity Using Cryopreserved Precision Cut Lung Slices.
PG  - 225-33
LID - 10.1093/toxsci/kfv320 [doi]
AB  - To assess chemical toxicity, current high throughput screening (HTS) assays rely 
      primarily on in vitro measurements using cultured cells. Responses frequently 
      differ from in vivo results due to the lack of physical and humoral interactions 
      provided by the extracellular matrix, cell-cell interactions, and other molecular 
      components of the native organ. To more accurately reproduce organ complexity in 
      HTS, we developed an organotypic assay using the cryopreserved precision cut lung 
      slice (PCLS) from rats and mice. Compared to the never-frozen PCLS, their 
      frozen-thawed counterpart slices showed viability or metabolic activity that is 
      decreased to an extent comparable to that observed in other cryopreserved cells 
      and tissues, but shows no differences in further changes in cell viability, 
      mitochondrial integrity, and glutathione activity in response to the model toxin 
      zinc chloride (ZnCl2). Notably, these measurements were successfully miniaturized 
      so as to establish HTS capacity in a 96-well plate format. Finally, PCLS 
      responses correlated with common markers of lung injury measured in lavage fluid 
      from rats intratracheally instilled with ZnCl2. In summary, we establish that the 
      cryopreserved PCLS is a feasible approach for HTS investigations in predictive 
      toxicology.
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of the Society 
      of Toxicology. All rights reserved. For Permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Watson, Christa Y
AU  - Watson CY
AD  - *Molecular and Integrative Physiological Sciences Program, Department of 
      Environmental Health, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts 02115 and.
FAU - Damiani, Flavia
AU  - Damiani F
AD  - *Molecular and Integrative Physiological Sciences Program, Department of 
      Environmental Health, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts 02115 and.
FAU - Ram-Mohan, Sumati
AU  - Ram-Mohan S
AD  - *Molecular and Integrative Physiological Sciences Program, Department of 
      Environmental Health, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts 02115 and Department of Emergency Medicine, Beth Israel Deaconess 
      Medical Center, Boston, Massachusetts 02115.
FAU - Rodrigues, Sylvia
AU  - Rodrigues S
AD  - *Molecular and Integrative Physiological Sciences Program, Department of 
      Environmental Health, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts 02115 and.
FAU - de Moura Queiroz, Priscila
AU  - de Moura Queiroz P
AD  - *Molecular and Integrative Physiological Sciences Program, Department of 
      Environmental Health, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts 02115 and.
FAU - Donaghey, Thomas C
AU  - Donaghey TC
AD  - *Molecular and Integrative Physiological Sciences Program, Department of 
      Environmental Health, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts 02115 and.
FAU - Rosenblum Lichtenstein, Jamie H
AU  - Rosenblum Lichtenstein JH
AD  - *Molecular and Integrative Physiological Sciences Program, Department of 
      Environmental Health, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts 02115 and.
FAU - Brain, Joseph D
AU  - Brain JD
AD  - *Molecular and Integrative Physiological Sciences Program, Department of 
      Environmental Health, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts 02115 and.
FAU - Krishnan, Ramaswamy
AU  - Krishnan R
AD  - Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, 
      Massachusetts 02115.
FAU - Molina, Ramon M
AU  - Molina RM
AD  - *Molecular and Integrative Physiological Sciences Program, Department of 
      Environmental Health, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts 02115 and rmolina@hsph.harvard.edu.
LA  - eng
GR  - P30 ES000002/ES/NIEHS NIH HHS/United States
GR  - T32 HL007118/HL/NHLBI NIH HHS/United States
GR  - ES00002/ES/NIEHS NIH HHS/United States
GR  - HL007118/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20151229
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Chlorides)
RN  - 0 (Zinc Compounds)
RN  - 86Q357L16B (zinc chloride)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chlorides/toxicity
MH  - *Cryopreservation
MH  - Epithelial Cells/drug effects/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Lung/cytology/*drug effects/metabolism
MH  - Male
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mice, Inbred C57BL
MH  - Monocytes/drug effects/metabolism
MH  - Organ Specificity
MH  - Oxidative Stress/drug effects
MH  - Primary Cell Culture
MH  - Rats, Wistar
MH  - Toxicity Tests/*methods
MH  - Zinc Compounds/toxicity
PMC - PMC5009619
OTO - NOTNLM
OT  - cryopreservation
OT  - high throughput screening
OT  - organotypic
OT  - precision cut lung slices
OT  - toxicology
OT  - zinc chloride
EDAT- 2016/01/01 06:00
MHDA- 2016/12/15 06:00
PMCR- 2017/03/01
CRDT- 2016/01/01 06:00
PHST- 2017/03/01 00:00 [pmc-release]
PHST- 2016/01/01 06:00 [entrez]
PHST- 2016/01/01 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - kfv320 [pii]
AID - 10.1093/toxsci/kfv320 [doi]
PST - ppublish
SO  - Toxicol Sci. 2016 Mar;150(1):225-33. doi: 10.1093/toxsci/kfv320. Epub 2015 Dec 
      29.