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question about measuring changes in rate of cell proliferation

Brian Scott brians at interlog.com
Fri Apr 3 01:15:37 EST 1998

Hello folks.  I've got a question about determining changes in the rate of
proliferation of neuronal precursors...specifically in the dentate gyrus of the
rat brain.

Numerous studies have used the thymidine analog bromodeoxyuridine (brdu) to
indicate which cells were undergoing mitosis.  Presumably, the more brdu
labelled cells you see, the more cells are undergoing mitosis.  That's what many
papers have assumed.  My question concerns the interpretation of increased
numbers of brdu+ nuclei in tissue slices from a treatment group compared to a
control group.  If you have more (or less) brdu+ nuclei in tissue slices from a
treatment group it could be due to a greater number of cells in mitosis.  On the
other hand, if your treatment affects the length of the cell cycle...or
specifically the length of the DNA synthetic phase, couldn't that increase (or
decrease) the number of brdu+ cells you see in a given slice without the actual
number of proliferating cells being changed?

So, if the DNA synthetic phase is lengthened, you are more likely to label
nuclei with an injection of brdu so you would see more brdu+ cells in your
slices.  Couldn't the length of the DNA synthetic phase be altered without
changing the number of proliferating cells?  Could drugs or physiological
changes (e.g. hormones, growth factors) do this?

In order to see if there is an actual change in the number of proliferating
cells wouldn't you have to make sure that ALL the proliferating cells in the
system are brdu labelled?  This would give you the growth fraction of the
population and if this is different then there truly is a change in the number
of proliferating cells. 

I just want to know if I'm thinking about things in the right way.


  Brian Scott          |  Department of Physiology
  brians at interlog.com  |  University of Toronto, Canada      

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