RE: Stable Reciprocal Translocation Blood Test

["Carlisle, Sara" <carlisles@aecl.ca>]

I asked around about the sensitivity of the reciprocal translocation
test, and apparently you can "just" see (don't know about the stats,
however) a difference in the frequency of reciprocal translocations
following an acute dose of about 25 cGy.  This is based on in vitro
experiments with irradiated blood.  For an individual, detecting this
sort of difference would depend on whether you had a good control
estimate for the frequency of reciprocal translocations in that
individual prior to receiving the dose. 

I'm sure if you looked at enough slides, you could get your 95%
confidence level at 15 cGy, although you might drive the technologist
who sits at the microscope insane - the lower the dose, the more cells
you have to look at to find enough chromosomal aberrations to get the
required statistical power.  Since the rate of induction of reciprocal
translocations is thought to be similar to the rate for dicentrics, 15
cGy with 95% confidence must be the reasonable limit to the number of
slides you can get someone to look at before they quit in desperation.

Reciprocal translocations are mostly used to estimate cumulative
life-time dose, although it must be noted that other sources of DNA
damage may contribute to the frequency.  Dicentrics, on the other hand,
are transient abnormalities and are not stably inherited - cells
carrying them are lost from the circulating blood cell population so
dicentrics are more useful for assessing recent exposures.  The
frequency of dicentrics will reach a maximum shortly (?hours) after
exposure, and then decline due to turnover of the white blood cells
(half-life of about 3 - 3.5 years).

Since the rate of induction of the two types of abnormalities is
apparently about the same, looking at the current frequency of
reciprocal translocations compared to that of dicentrics gives a
reasonable indication of past damage vs. recent damage.

Hope this is useful.

Sara Carlisle
Radiation Biology and Health Physics Branch
Chalk River Laboratories

phone (613) 584-8811 extn. 3667
email carlisles@aecl.ca


> ----------
> From: 	Pickett, Bruce D[SMTP:Bruce.Pickett@PSS.Boeing.com]
> Sent: 	March 2, 1998 2:53 PM
> To: 	Multiple recipients of list
> Subject: 	RE: Stable Reciprocal Translocation Blood Test
> 
> Sara,
> 
> Thanks for the terriffic information.
> 
> I understand that dicentric chromosomal tests can detect doses greater
> than about 15 Rad (0.15 Gy) whole body at a 95% confidence level. Do
> you
> know what the sensitivity for the translocation test is? Is there any
> reason for choosing the dicentric test over the translocation test, or
> vice versa?
> 
> Thanks,
> 
> Bruce Pickett
> bruce.d.pickett@boeing.com
> 
> > ----------
> > From: 	Carlisle, Sara[SMTP:carlisles@aecl.ca]
> > Sent: 	Monday, March 02, 1998 8:28 AM
> > To: 	'radsafe@romulus.ehs.uiuc.edu'
> > Cc: 	'Bruce.Pickett@PSS.Boeing.com'
> > Subject: 	RE: Stable Reciprocal Translocation Blood Test
> > 
> > Bruce:
> > 
> > A stable reciprocal translocation blood test looks at the frequency
> of
> > "reciprocal translocations" in circulating white blood cells.  In
> > cells,
> > the genetic material, DNA, is packaged into sub-units called
> > chromosomes. When DNA is damaged there can be rearrangement of these
> > sub-units, leading to events collectively known as chromosomal
> > aberrations. Certain classes of chromosomal aberrations (i.e.
> > reciprocal
> > translocations) are stable and can be used to determine lifetime
> > cumulative radiation exposures. Other chromosomal aberrations, such
> as
> > dicentric chromosomes, can be used to assess recent exposures -
> these
> > aberrations are not stably inherited, since they affect partitioning
> > of
> > genetic material between daughter cells during cell division.
> > Chromosomal aberrations are the end-points traditionally measured in
> > biological dosimetry and have, for example, been used extensively in
> > studies of the Japanese Atomic Bomb survivors. 
> > 
> > To measure chromosomal aberrations, white blood cells are isolated
> > from
> > a blood sample, stimulated to divide (with PHA -
> phytohaemagglutanin)
> > and then treated with a chemical (colcemid) to stop cell division at
> a
> > point where individual chromosomes can be seen (metaphase).  The
> > chromosomes are stained with dyes, and examined by a cytogeneticist
> > who
> > looks for abnormal chromosomes. Recent advances in molecular biology
> > allow specific chromosome pairs to be stained with dyes that
> > differentiate them from the remaining chromosomes (chromosome
> > painting),
> > which makes detection of reciprocal translocations much easier than
> > traditional non-specific staining techniques, which relied on
> > recognition of changes in complex banding patterns on the
> chromosomes
> > for detection of chromosomal abnormalities - a very tedious exercise
> > that required a very experienced cytogeneticist.
> > 
> > Hope this helps. I'm not actually doing these assays myself, but
> staff
> > here at AECL are doing research involving reciprocal translocation
> > assays on blood samples.  If my explanation is too full of molecular
> > biological jargon, let me know and I'll give it another shot.
> > 
> > Sara Carlisle
> > Radiation Biology and Health Physics Branch
> > Chalk River Laboratories
> > 
> > phone (613) 584-8811 extn. 3667
> > email carlisles@aecl.ca
> > 
> > > ----------
> > > From: 	Pickett, Bruce D[SMTP:Bruce.Pickett@PSS.Boeing.com]
> > > Sent: 	March 2, 1998 10:42 AM
> > > To: 	Multiple recipients of list
> > > Subject: 	Stable Reciprocal Translocation Blood Test
> > > 
> > > Does anyone know what a "stable reciprocal translocation blood
> test"
> > > is?
> > > Please provide any details which you can think of in your
> response.
> > > 
> > > Bruce Pickett
> > > bruce.d.pickett@boeing.com
> > > 
> > 
>