Re: Help about BrdU

From: Derek Davies (daviesd2@icrf.icnet.uk)
Date: Wed Apr 11 2001 - 10:36:36 EST


Hi Martha,

THere are a number of things to bear in mind with the BrdU technique.
One is that it is only true to say that labelled cells are in S phase when
the pulse with BrdU is short. The longer it is the more likely that
labelled cells will have passed through S into G2 and even back round to
G1 again. In general a pulse of 30-60 minutes will give a reasonable
percentage of labelled cells. An 8 hour pulse will detect cells that
were near the end of replication at the beginning of the pulse and these
will have continued during the time BrdU was present to end up
elsewhere. The BrdU technique is quite versatile as it allows you to
address different questions depending on your labelling and/or sampling
time.

If, after 8 hours, you see low levels of incorporation and you are sure
that your population is expanding, then there may be a technical
problem. If you are using the acid denaturation method, you must be
quite stringent with your washes after HCL; I find that a minimum of
three PBS washes after spinning the acid off is required - you need to
make sure that your primary antibody isnt denatured!

There is also a balance between unwinding enough DNA to expose the BrdU
to the antibody and not doing too much so that the resolution obtained
with your DNA dye is lost. Too high a molarity or too lonmg in acid will
lead to loss of DNA histogram resolution. I normally find that 15-30
mins in 2N HCL is a good starting point.

Hope that helps a bit!

Derek

On Tue, 10 Apr 2001, Martha Mesa - Microbiologia wrote:
> In my laboratory, I am studying the effect of some compounds on tumoral
> cell cycle by PI staining. In order to know if the antitumoral effect
> observed is due to a decrease in DNA synthesis I am trying to set the
> BrdU incorporation assay, by I have several questions; some of them
> are:
>
> 1. For cells with doubling time of 22  (k562)  and 72 hours (KG1a), how
> long must be the pulse? I have used BrdU 10 uM for 8 hours;  I have
> only obtained low intensity in fluorescence some times.
>
> 2.Some protocols recommend more HCl. I have used 2M, 3M and 4M. With 4M
> the BrdU signal improves but phase resolution with PI disappear.  I
> would like to > know the effect in each phase; how can I obtained
> that?
>
> Thanks in advance,
>
> Marta Mesa
>
>

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Derek Davies                       Voice: (44) 020 7269 3394
FACS Laboratory,                   FAX: (44) 020 7269 3100
Imperial Cancer Research Fund,     e_mail: derek.davies@icrf.icnet.uk
London, UK			   mobile: 07790 604112

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