Effects of prenatal irradiation with special emphasis on late effects

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Commission of the European Communities
radiation protection
Effects of prenatal
irradiation with special emphasis
on late effects Commission of the European Communities
radiation protection
Effects of prenatal
irradiation with special
emphasis on late effects
EULEP symposium
29 July 1982, Bordeaux (France)
edited by:
C. Streffer
Universitätsklinikum, Institut für
medizinische Strahlenphysik und Strahlenbiologie
Essen, Federal Republic of Germany
G. Patrick
MRC Radiobiology Unit
Harwell, United Kingdom
This symposium was organized by the European late effects project group (EULEP) and co-sponsored
by the Commission of the European Communities
1984 EUR 8067 EN Published by the
COMMISSION OF THE EUROPEAN COMMUNITIES
Directorate-General
Information Market and Innovation
Bâtiment Jean Monnet
LUXEMBOURG
LEGAL NOTICE
Neither the Commission of the European Communities nor any person acting on behalf of the
Commission is responsible for the use which might be made of the following information.
Cataloguing data can be found at the end of this publication
Luxembourg: Office for Official Publications of the European Communities, 1984
ISBN 92-825-4173-8 Catalogue number:
© ECSC-EEC-EAEC, Brussels · Luxembourg, 1983
Printed in the FR of Germany Ill
PREFACE
The study of late effects following prenatal irradiation represents a
new area of co-operative research for the European Late Effects Project
Group (EULEP). The scope of this activity, under the chairmanship of
Professor Dr. Streffer, is indicated by the content of this symposium, which
was held in conjunction with the European Society of Radiation Biology
meeting in Bordeaux.
As explained in the chairman's introduction, studies on thé effects of
radiation in utero have progressed lately as a result both of new
experimental techniques and of new insights into which effects are relevant
for man. The four following papers analyse the action of radiation at the
pre-implantation stage, using in vitro as well as in vivo techniques. The
remaining studies, on the effects of radiation exposure at later stages of
gestation, concentrate not so much on malformations in development, but
bring together other important recent advances, such as effects on the
central nervous system. These are analysed here both in the mouse and in
human experience. The overall risks in the case of man are further analysed
in the clinical context of follow-up studies after diagnostic exposures
in utero. Experimental studies are also presented on carcinogenesis
following prenatal irradiation, including that from incorporated
radionuclides. Consideration is given to the overall effects of
incorporated tritium, and there are separate accounts of work on the
transfer of different radionuclides from the mother to the developing
organism in utero.
The editors wish to express their warm appreciation to all who took
part in the symposium; also to Miss Deborah Walker for preparing the
typescripts; and to the Commission of the European Communities for
supporting the publication of these proceedings.
G. PATRICK IV
EULEP SYMPOSIUM: _ Summary, Sheet
This S5rmposium by the European Late Effects Project Group
(EULEP) was held in Bordeaux following the annual meeting of
the European Society f or RadiâtJ on Biology. It brings together
both experimental studies and observations in man concerning
the various effects of prenatal irradiation. After an intro
duction outlining the areas in which recent advances have been
made, there are four papers analysing the lethal effects of ir
radiation at the earliest stages of development, using pre-
implantation mouse embryos cultured in vitro as well as grown
in vivo. The remaining studies, on the effects of exposures
at later stages of development, concentrate not so much on
malformations that may be induced, but bring together other
important recent advances, such as our understanding of
disturbances in the developing central nervous system. These
are analysed both in the mouse and in the human experience, in
particular in A-bomb survivors. Trie overall risks in the case
of man are further analysed in the clinical context of follow-up
studies after diagnostic exposures in utero. Experimental s are presented on carcinogenesis in animals irradiated
prenatally, including irradiation from incorporated radio
nuclides. Particular consideration is given to the overall
effects of incorporated tritium, ranging from cytogenetic
aspects to carcinogenesis as well as non-neoplastic late effects.
Separate papers are included on the transfer of different
radionuclides from the mother to the fetus, providing information
necessary for the estimation of the absorbed dose. CONTENTS
Introduction: C. Streffer
Changes in Sensitivity of Mouse Embryos during the Pronuclear
and the 2-Cell Stage
T. Yamada and 0. Yukawa
In vitro Studies on the Radiosensitivity of the Mouse Zygote 19
P. Jacquet, G. Kervyn and G. De Clercq
Development of Cytogenetic Effects and Recovery after
Irradiation of Preimplantation Mouse Embryos 31
M. Molls, C. Streffer, B. Fellner, U. Weissenborn,
M.L. Steimann and W. Breipohl
Combined Effects after Exposure during the Preimplantation 49
Period
W.-U. Müller and C. Streffer
Postnatal Development of the CNS after Prenatal Irradiation 61
G. Konermann, B. Metzger and E. Roser
Neuroblast Destruction in Mouse and Man after Neutron 77
Irradiation in utero
S. Antal and H.H. Vogel
Long-term Effects after Prenatal Irradiation 89
W. Schmahl
Neoplastic Effects after Prenatal Irradiation 101
G. Walinder and C. Rönnbäck
"Tritox" - A Multiple Parameter Evaluation of Tritium Toxicity 117
A.L. Carsten VI
The Longterm Effects of Tritium Incorporated in utero 143
Β.E. Lambert and M.L. Phipps
Exchange and Transfer Mechanisms of Radioactive Compounds 15o
between the Mother and the Developing Offspring in utero-
Review of the Experimental Literature
F.E. Stieve
Diaplacental Transfer and Distribution of Some Radionuclides 18 3
in Fetal Organs at Different Stages of Gestation
Experimental Results
R. Senekowitsch and H. Kriegel
The Pathogenesis of Microcephaly with Mental Retardation 199
J. Dobbing
Human Experience of Radiation Damage following Prenatal 213
Exposure: its Interpretation and Implications
R.H. Mole
Findings in Children after Radiation Exposure in utero from 229
Xray Examination of Mothers: Results from Children Studied
after One to Ten Years
K. Neumeister and S. Wässer INTRODUCTION
C. Streffer
Institut far Medizinische Strahlenphysik und Strahlenbiologie,
Universitätsklinkikum Essen,
Hufelandstr. 55, D-4300,
Federal Republic of Germany
During the prenatal development of a mammalian organism the dominant
processes are cell proliferation, differentiation and migration. From the
fertilized omnipotent oocyte, which carries all the genetic potential to
develop an integrated mammalian organism, a child is born in the case of man
after nine months of pregnancy with around 10 cells. Thus the number of
cells increases by 12 orders of magnitude during this period, while during
subsequent human life the cell mass further increases only by a factor of
20. Although cell turnover may be higher during postnatal life,
considerable cell loss is also observed during most phases of prenatal life.
On the basis of such considerations it is not surprising that exogenous
physical and chemical agents can interfere with developmental processes with
a high degree of sensitivity.
Mammalian development is usually divided into three periods: during the
preimplantation period cell proliferation is the dominant process, with some
differentiation. After implantation of the embryo into the uterus, the
induction and formation of differentiated tissues and organs commences and
is carried out during the period of major organogenesis. This period is
followed by fetogenesis, during which the main occurrence is growth of the
fetus. However, although the macroscopic appearance of the fetus in the
early fetal period already resembles the new-born, many developmental
processes still occur during the whole fetal period, especially in the
central nervous system. While the duration of the preimplantation period is similar in most
mammalian species including man, it varies for major organogenesis and
differs to an even larger extent for the fetal period (Table). Most
information about radiation effects stems from experiments with rodents. To
extrapolate from such experimental data to the situation in man is
apparently more appropriate for early prenatal development than for the
later periods. Froml data with mice and rats it has been
concluded that the period up to the end of major organogenesis and the
beginning of the fetal period is the most radiosensitive, so that in
regulations for radiation protection, dose limitations have been made for
the first two months of pregnancy but not for the later period.
More recent data have