RE: Down Syndrome and Radiation Exposure

["Franta, Jaroslav" <frantaj@aecl.ca>]

> Carlisle, Sara [carlisles@aecl.ca] wrote on Thursday, June 10, 1999 2:56
> PM:
> 
> Teratogenic effects are non-genetic effects induced by some factor, such
> as the abnormal limb development induced by thalidomide without altering
> the DNA.  Down Syndrome, on the other hand, is the result of genetic
> abnormality - in particular, having three copies of a region of chromosome
> 21, so is not a teratogenic effect but a genetic effect.
> 
> Although it has sometimes been suggested that Down Syndrome may increase
> due to radiation, evidence does not seem to support this.  See, for
> example, Johnson, K.C., and Rouleau, J. (1991) Tritium releases from the
> Pickering nuclear generating station and birth defects and infant
> mortality in nearby communities 1971-1988, AECB report INFO-0401. In this
> study of the
> population of Pickering, Ontario, Canada (1971-1988), no evidence of
> increased incidence for 21of 22 birth defects was found, and while a
> "cluster" of Down's syndrome cases near Pickering were observed, the
> affected births were usually followed in time by tritium releases, ruling
> out causation.  Similarly, I don't believe the Atomic Bomb Survivor
> follow-up has found an association between Down Syndrome and radiation
> exposure.
> 
> Mental retardation and small head size, however, is associated with in
> utero exposures between 8 and 15 weeks after fertilization, and to a
> lesser extent from 16 to 25 weeks.  Such effects are associated with doses
> greater than about 10 cGy (see Yamazaki and Schull, 1990, JAMA 264:
> 605-609 - I'm sure there are more recent references, but this was the only
> one I could dig out on short notice).  These effects are teratogenic
> rather than mutagenic, and appear to be associated with disruption of
> neuronal migration during development.
> 
> <><><><><><><><><><><><><>
> 
It may interest you to know that...
....in response to my own question to RERF ( the Radiation Effects Research
Foundation, formerly ABCC -- the Atomic Bomb Casualty Commission ) earlier
this year,

> > In your answer to Question 4, "What health effects have been seen among
> > persons who were exposed while still in their mothers' wombs?" there is
> no
> > mention of teratogenic effects such as have resulted in the case of some
> > chemicals like thalidomide. Is this an oversight or is there a definate
> > absence of teratogenic effects such those one sees with some chemicals ?
> 
> 
> the RERF WWW Committee[SMTP:research-info@rerf.or.jp] wrote on Monday,
> January 25, 
> 
> Dear M. Franta,
> 
>   Thank you for your correspondence on January 4. We apologize for taking
> so long to reply. As your question is not the area of expertise of anyone
> currently on site, we consulted an authority on human genetics who has
> been affiliated with the Radiation Effects Research Foundation from its
> early days.
> 
>   His comments in regards to your question are reproduced below. We hope
> this provides some satisfactory answer to your question.
> 
> RERF WWW Committee
> 
> --------------------
....
.....unlike the situation with respect to ionizing radiation and exposure of
the embryo or fetus of women who were pregnant at the time of the atomic
bombing (only a few thousand such women), the number of pregnant women who
were using thalidomide was very much greater, literally tens of thousands
since it was the most commonly employed drug in Europe for "morning
sickness".  Hence the population at risk was very large in one instance, and
relatively small in the other.   
....
> 	As to the effects of exposure to ionizing radiation on the fetus, we
> know that such exposure impairs cortical function and in a variety of
> ways.
> Such exposure may also increase the frequency of congenital dislocation of
> the hip, although the evidence for this is not terribly strong.  As to
> other malformations, we have little or no information.  The conditions in
> Hiroshima and Nagasaki in the first year following the bombing were
> chaotic
> and no systematic surveys of substantial size were undertaken.  However,
> there were a few small scale studies that are described in a book edited
> by Ishikawa and Swain.  These studies do not tell us much about the risk
> of malformation; however, they do support the notion that a highly
> significant number of pregnancies (under 16 weeks of gestation at the time
> of exposure) were lost.  This loss is also reflected in the RERF data when
> one looks at the ages at exposure of the in utero clinical sample.  This
> sample includes far fewer individuals exposed under 16 weeks of age than
> would be expected if pregnancy loss was independent of age at exposure.
> 
> 	One might wonder why the experimental data clearly show a
> teratogenic effect of exposure whereas the human data are far less
> compelling.  I suspect that it may be a "sampling problem."  For example,
> experimental
> studies with rodents have shown that harelip (with or without cleft
> palate)
> is markedly increased by exposure to radiation, but this has not been seen
> in humans.  However, if one assumes that radiation can only impair those
> embryological processes that are ongoing at the time of exposure, then
> time
> of exposure is critical to the results one obtains.  Animal experiments
> are
> so timed to result in exposure in just the short critical window when the
> palatal shelves are closing.  In the human, however, age at exposure was
> governed by chance.  Closure of the palatal shelves in the human fetus
> begins at about the eighth week and requires only a few days.  Exposure
> after the closure will not give rise to harelip (with or without cleft
> palate), and it is questionable whether exposure prior to initiation of
> the
> closure process would give rise to harelip although it might produce some
> other defect.  Thus relatively few fetuses would have been exposed at a
> time when impairment of the closure of the palatal shelves was likely.
> More specifically, among the roughly 1600 members of the clinical in utero
> sample, only about 500 were exposed to more than 1 cGy.  If one assumes
> that the distribution of these 500 cases is roughly rectangular, then only
> about 13 would have been exposed in any given week of gestation.  If
> vulnerability lasts only a week and is dose dependent, then with only 13
> or
> so fetuses at risk it should not be surprising that we cannot show an
> increase in harelip following maternal irradiation.  This same argument
> can
> be applied to essentially all other common malformations, such as
> anencephaly, spina bifida, and the like.  But in this context the
> development of the neocortex is different.  It is far more complicated
> (and
> hence more opportunities for damage) and it proceeds over a much longer
> period of time.
> 
> --------------------
...the RERF web site is at http://www.rerf.or.jp/eigo/experhp/rerfhome.htm

Jaro

frantaj@aecl.ca

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