PI staining & cell cycle analysis

From: Roger Smith (rosmith@pop.tamu.edu)
Date: Thu May 06 1999 - 11:24:31 EST


dear group,

I have a user who is trying to synchronize different cell lines in G1 to
perform electrophoretic mobility shift assays on those cells. most of the
lines can be synchronized to 90-95% G1 (by ModFit LT) by serum starvation.
one is being recalcitrant with about 85% in G1 and 15% in G2/M, although
earlier it was behaving as well. she feels she must have >90% in G1 for her
assays. in an effort to improve the situation, she ordered a new stock of
the cell line (MFC-10) and started over. they didn't work well either. but
they are also doing something that doesn't make a lot of sense to me. since
we run some, but not a whole lot of PI-stained samples, i am stumped.

in a plot of PI-width vs. PI-area, the cells are now spreading out
horizontally, showing a great variation in PI-width. microscopically, they
are very heterogeneous in size. but on the width vs. area plot, there is
also a slope to the line of cells in G1 and those in G2/M; there is a
slight increase in PI-area associated with the increase in PI-width. My
questions are:

1. could differences in chromatin condensation be responsible for this
correlation? if not, what else? is there any way to fix this with her cells?

2. how do i model this situation? the effect is to increase the CV of the
G1 peak on the PI-area histogram to about 5-6%. visually, the width vs.
area dot plot is very tight. it seems that i could use WinList to do
software "compensation," but somehow that feels wrong in this situation.
and i am not sure that WinList's compensation algorithm compensation will
model this type of correlation. still, it is a mathematical remedy for a
biological predicament, and that makes me uncomfortable.

oh, and she is saturating the DNA with PI, because she has even tried
centrifuging the cells, resuspending in the PI stain and re-incubating
overnight. the plots are the same

thanks in advance,

Roger Smith
Dept. Veterinary Pathobiology
Texas A&M University

Phone:  (409) 845-5167
Fax:    (409) 862-1088
e-mail: rosmith@cvm.tamu.edu



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