Re: Do PI concentrations vary for measuring cell viability and DNA analysis???

From: Mark Kukuruga (kukuru@med.umich.edu)
Date: Thu Jun 21 2001 - 09:29:09 EST


Rana,
PI stains double-stranded nucleic acids.  If we want to resolve cell cycle compartments,
we typically use 20-50 ug/ml (I've gone as low as 10) as a staining concentration.
If you do the comparison, you'll find that this relatively broad range will yield
comparable results.  Much higher, and you start to lose resolution . . . lower, and you
may no longer be stoichiometric . . . i.e., you may not stain all cells as uniformly
as you'd like, and G1/G2M ratios will suffer.  50 ug/ml is an accepted concentration
for cell cycle staining.
However, if all you need is a viability marker, add just enough to resolve live
from dead.  And, since this measurement is usually done log amplified, only a little
is needed.
There are applications where sub-optimal PI concentrations are necessary.  If, for
example, you want to look at other nucleic acid-associated markers (say, incorporated
BrdU, or some DNA associated protein) with green fluorescent dyes - - like FITC -
- , you may actually quench your signal with too much PI.  Here, stoichiometry is
sacrificed for green signal resolution . . . in this case, all you want is a G1 and
G2M position indicator, and 1 to 5 ug/ml PI will accomplish that.
Adding lower amounts of PI will better allow simultaneous analysis of phycoerythrin
conjugates . . . signal crossover is far more manageable.
Adding low amounts also helps with visualizing co-stains via microscopy.  If, for
example, you want to look at PI versus some green fluorescent marker . . . too much
PI will overwhelm/mask the green signal.
Bottom line . . . use the concentration that's appropriate for the application.
50 ug/ml is a standard for cell cycle.  Other applications may require changes in
this empirically defined optimal concentration.  Using PI at 1 ug/ml (or even less)
will work as a viability indicator.
MAK.

--
Mark A. KuKuruga, Managing Director
University of Michigan Flow Core
7416 CCGC 0946
(734) 647-3216, fax (734) 936-7376
kukuru@umich.edu


>>> Rana Nagarkatti <rana_nagarkatti@usa.net> 06/19/01 05:06PM >>>

Dear Group,
 I was wondering if the above queston is actually true. The reason being that
I had done some calculations regarding the final conc of PI in various
protocols used for Viability and DNA analysis. and found that ususally for DNA
50ug/ml is the required conc ( for Flow- may be to maintain equilibrium in the
stream etc but any ideas for fluorimetry???)and for viability it is around
1ug/ml. What is the reason? Do higher conc of PI in the staining buffer mean
that more PI will enter the cells or is the cell totally impermeable to the
PI. or that the PI conc used for viability has been standardized based on a
concurrent experiment with say trypan blue or other methods? And how does time
of incubation after adding the dye relate to the conc. After all both the
methods are based on the same prinnciple that PI binds to DNA. Are there any
simple proportionalities involved here eg more the dye less the time or mmore
the dye more enters into the cells etc.
Thanks in advance for all the tips.
Rana Nagarkatti

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