RE: Any thoughts on the detection of Ionizing radiationeffects in rats

From: Gerhard Nebe-von-Caron (Gerhard.Nebe-von-Caron@Unilever.com)
Date: Wed Oct 03 2001 - 05:22:22 EST


Hi Richard

Unfortunately the photo was missing. Perhaps you might want to embed a link
instead

The paper actually discusses the binding to mitochondrial DNA, but for imaging
or as an application with the LSC this should not be a problem.

Several years ago I looked at "non-specific" binding of avidins and found in my
case that high salt (10x physiological NaCl) seemed to significantly reduce it
on skin samples which I attributed to the neutralising effect of high salt on
electrostatic binding. Perhaps you could a comment on that possibility.


For those interested you can have a look at the kit for measuring it by flow
http://www.kamiyabiomedical.com/04LifeScienceResearchProducts/PackageInserts/3/DN001.htmor
buy it a bit cheaper from your favourite supplierRegardsGerhard Nebe-von-CaronResearch
ScientistApplied Science & Technology GroupSEAC - Safety and Environmental Assurance
CentreUnilever Research, Colworth Laboratory, Sharnbrook, UK - MK44 1LQTel: +44 (0)1234
264822, Fax: +44 (0)1234 222552E- mailto:Gerhard.Nebe-von-Caron@unilever.com-----Original
Message-----From:      Richard Haugland [SMTP:richard.haugland@probes.com]Sent:
Wednesday, October 03, 2001 2:53 AMTo:	Gerhard Nebe-von-CaronCc:	dick@probes.com;
Cytometry Mailing ListSubject: Re: Any thoughts on the detection of Ionizing
radiationeffects  in ratsGerhard,That's an interesting paper whose significance I
had missed. We have not testedthat property fo avidins. Oxidized guanosine has one
ring that looks sort oflike the urea part of biotin but I am surprised that the
affinity is highenough because it has the ribose off one of those nitrogen atoms
and the secondaromaticring of the purine bears little resemblence to the rest of
biotin.We see nice selective staining of mitochondria by avidins in total absence
ofbiotinylated probes so there could be difficulty staining 8-hydroxyguanosincein
cells with avidins if there is only low-level damage. It is definitely apotential
problem using any avidin or streptavidin conjugate with fixed cellpreps thatfew
people are aware of.[Photo: 46KB]The intermediate filaments in bovine pulmonary artery
endothelial cells,localized using anti-desmin					antibody
(mousemonoclonal 131-15014), which was visualized with Alexa Fluor 647 goatanti–mouse
IgG conjugate. Endogenousbiotin in themitochondria was labeled with an Alexa Fluor 546
streptavidin conjugate	and DNA in the cell was stained withblue-fluorescent DAPI.Gerhard
Nebe-von-Caron wrote:> It would be interesting to compare that with the paper
of>http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9448838&dopt=Abstractas>
they claim the "Direct detection of 8-oxodeoxyguanosine and 8-oxoguaninebyavidin and>
its analogues" as a measure of oxidative DNA damage. It looksverystraightforward>
but suggests you should not block with streptavidin but justmeasure it's>
binding.RegardsGerhard-----Original Message-----From:	     Richard Haugland>
[SMTP:richard.haugland@probes.com]Sent:        Friday, September 28, 2001>
8:20 PMTo:   Cytometry Mailing ListSubject:  Re: Any thoughts on the detection>
of Ionizing radiationeffects  in ratsThere is a possibility that the reagent>
ARPhttp://www.probes.com/servlets/product?region=Select+Region&item=10550would>
be useful.This biotin derivative reacts with abasic sites of nucleic
acids> (nucleic acidsthat havelost their base but not the backbone
structure> and thus generate aldehydes.ARP has been used to detect this event in
living>cells:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10639140&dopt=Abstractand>
abasic sites produced by
reactive-oxygen>specieshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1567824&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8347625&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11020331&dopt=AbstractIonizing>
radiation also produces abasic sites. Use of agreen-fluorescentstreptavidinconjugate>
should work in flow cytometry (or imaging); however, I recommend thatyoublockendogenous>
biotin first with streptavidin followed by excess biotin.Mitochondria,inparticular,>
have endogenous biotinylated proteins that could interferewithlow-leveldetection. Cells>
with endogenous damage by ROS may also react as positive so youwillneedcontrols.Simon>
Monard wrote:> Hi>  Could you look for chomosome damage by flow cytometry. Idon't>
know how rarechromosome>  damage would be. Its not very hard to preparechomsome preps>
from rats,either con>  A stimulated blood or perhaps you could look atgranukoma pouch>
assay cells.Just>  a thought. We made some chromosome paints for rat andtried to look>
forabnormal>  chomosomes by microscopy also.> Simon> FLOWers>>	       I amin need of>
some help.>>  We want to look at the protective effect of drug X on radiationinduced>>
damage in the rat, by Flow Cytometry.>	Does anyone have any thoughts??>> Iknow this>
is potentially a  very broad subject, but I would appreciate any> thoughts onpotential>
avenues of approach>> > thank you for your time and help
> >
> > Philip Barren



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