Re: PI deactivation

From: Howard Shapiro (hms@shapirolab.com)
Date: Sat Apr 15 2000 - 19:32:10 EST


Keith Bahjat writes (re propidium toxicity)-

>How dangerous is a membrane impermeable dye?? Unless it can resurrect dead
>epithelial cells, it should not have access to the DNA of living cells, and
>thus shouldn't be much of a safety hazard.
>
>We always wipe everything down with ethanol, but I've yet to see data
>showing membrane impermeable DNA intercalating dyes cause problems for
>living cells. I think the MSDS claims are based on a general fear of
>anything that has the word "DNA" in it.
>
>Anyone have data to contradict this??

The funny thing is that, according to data on Molecular Probes' safety
sheets, the LD50 in mice for the propidium, which is supposedly
membrane-impermeant, is lower than that for ethidium, which is
membrane-permeant (ethidium is usually pumped out of viable cells, which is
why it often seems to work in dye-exclusion viability tests).  So, either
propidium isn't membrane-impermeant all the time, or it may be metabolized
in vivo to something which is.

Note that the terms I use here with respect to the dyes are permeant and
impermeant, describing things which get through and don't, as opposed to
permeable and impermeable, describing membranes which do and don't let
things get through.  Membranes are normally impermeable to propidium, which
is impermeant to intact membranes.

The other ringer in this game is that there are circumstances under which
cells become transiently permeable to propidium and structurally similar
dyes (e.g., TO-PRO-1 and TO-PRO-3) without loss of viability.  This happens
during scrape loading of cells with various normally impermeant compounds,
during electroporation and other treatments used in transfection, and, in
at least some bacteria, after exposure to sublethal concentrations of some
antibiotics (Novo et al, Antimicrobial Agents and Chemotherapy 44:827-34,
2000).  The bacterial response is interesting because it may provide a back
door through which compounds with minimal host toxicity may be introduced
to kill otherwise antibiotic-resistant organisms.  If host cell
permeability is variable in the normal scheme of things, this therapeutic
approach becomes harder to implement, but we're still looking into it.

All that said, while I wouldn't substitute propidium for paprika, I
wouldn't get paranoid about it, either.

-Howard



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