Re: [Paraformaldehyde again.]:SOME SUGGESTIONS

From: john nguyen (ntvan@netscape.net)
Date: Sat Feb 06 1999 - 07:32:23 EST


Our Flow Cytometry Core facility at MD Anderson Cancer center over the year
had about a dozen users who were interested in measuring the expression of
Green fluoresrescence protein in conjunction with another phenotype either a
surface marker, a marker for cell cycle distribution or a marker for apotosis.
In most experiments, the cells were transfected with GFP, used as monitor of
transfection, and a gene of interest were hematological cell lines  or
epithelial cell lines (HL60,MCF7, ovarian cell lines).  The idea was to study
if the expression of the gene of interest changed the expression of the
surface marker, cell proliferation or apoptosis.  GFP being used to
detect/prove successful transfection of the gene of interest, briefly a
function assay for the latter.
1)We have found that in all cases GFP were destroyed by even very mild
detergent(Tween 20 at 0.1%), Alcohol(Ethanol, Methanol)
2)Paraformaldehyde at 0.5% to 2 % preserved the expression of GFP at least
when comparing the percent of cells expressed before and after addition of
PFA.  The separation is about half a log poorer when Median /mean channel
number of the transfected and untransfected population before and after
addition of PFA was compared.  When the initial separation was 2 logs, this
was not a big problem, but if the GFP positive population was only a smear
barely above the background then the functional assay provided ambiguous
results.
3)When DNA profiles were required, we found that Propidium iodide gave very
low resolution profiles, i.e., CV of 6% or more but Hoeschst33242 worked if
you have dual laser system equipped with a well aligned UV laser.
4)Apoptosis assay using Tunel with fitc labeled nucleotides and exogenous
terminal transferase was slightly affected. The DNA profile with Hoeschst
33342 were good enough to quantitate apoptotic cells when apoptosis was well
advanced not in early apoptosis.  We are trying Anexin both green and red
Alexal with , still, disappointing results.

Hope that these will help

Ntvan(Not yet a guru!) 





 
Fluorescent protein
aaa001@agora.ulaval.ca wrote:

Dear Flowcyte gurus,

First I would like to thank all for their good advice with
paraformaldehyde. I found this List a week ago and really appreciate the
quality of the discussion and information.

I already searched the archive for my other question, but found nothing
about it. So here is my question : I am studying the expression of
constitutive GFP in mammalian cells. GFP will leak only from dead cells
when membrane integrity is loss (personal observation). As paraformaldehyde
permeabilize the cell membrane, will the GFP expressed will be entrapped
into cells or will GFP leak with time... Is there any way to prevent the
leakage of GFP after fixation ? Does high paraformaldehyde concentration
could be the solution (4%, 6%, 8% ?).

Thank you for your help.

Philippe-Alexandre

™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™

Philippe-Alexandre Gilbert
Institut de recherche en biotechnologie
Conseil National de Recherche du Canada
6100 Royalmount, Montreal, Quebec (Canada)
H4P 2R2




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