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Thyroid and its proximate tissues radiation dosimetry, stochastic and deterministic biological effects in human and model systems

Objective


1) Human data base for dosimetry
Thyroid mass, iodine kinetics have been defined in pregnant women and neonatals as a basis for dosimetry in such subjects.

2) Dosimetry
a) Foetal and neonatal dosimetry: have been defined using phantoms
b) Thyroid dose maps: have been established for all European countries allowing to estimate doses for population in case of nuclear accident.
c) Dosimetry: a new dosimetry unit has been proposed.

3) New models
a) 5 new models of transgenic mice expressing all types of thyroid tumors have been created
b) for radiation: human thyroid cell lines have been created but they dedifferentiated.

4) Oncogenesis
a) proliferation pathways of the thyroid have been defined.
b) proliferation mechanisms in tumors: first demonstration of the oncogenic transformation of a 7 transmembrane receptor (the TSH receptor) as the cause of 90% of hyperfunctioning adenomas and congenital hyperthyroidisms.

5) Oncogenes in experimental and human tumors
The patterns of expression of several oncogenes (ret, met) and of IGF1 have been defined in all types of human thyroid tumors and in murine tumors by immunohistochemistry and in situ hybridization.
This thyroid project as a whole has the objective of providing a more reliable scientific background against which public health officials, radiation protection organizations, and governments may evaluate risks from thyroid irradiation, establish dose limits, intervention levels and monitoring techniques appropriate to normal time and/or in the event of an accident. Within this general framework it is expected to:

a) advance foetal and neonatal thyroid dosimetry, and the dosimetry for sensitive target organs/tissues (e.g. brain), liable to be irradiated bY radionuclides contained in the foetal thyroid;
b) render more reliable the iodine kinetics models which underlav foetal and neonatal dosimetry;
c) provide studies of thyroid mass for different ages for use in dosimetry studies;
d) use newly available data on Thyroid Mass and Iodine Kinetics, to provide a country by country (and where necessary region by region) map for the probable distribution of Thyroid Radiation Dose throughout Europe after an incident in which radioiodine is inadvertently distributed;
e) derive a more scientifically reliable, and possibly easier to measure unit to incorporate this unit as part of the process of risk assessment and risk statement;
f) use newly created animal models and develop new animal models of transgenic mice for the study of the carcinogenetic process in thvroid in vivo and the role of environmental factors (eg. iodine supplv level of stimulation, etc);
g) establish tissue culture models for radiation induced thyroid diseases(including neoplasia);
h) use the human cell lines models for studying radiation and other mutagenic induced neoplasia. Definition of the steps of
immortalization.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

UNIVERSITE LIBRE DE BRUXELLES
Address
808,Route De Lennik 808 Campus Erasme - Building C
1070 Bruxelles
Belgium

Participants (2)

Federated Dublin Volontary Hospital
Ireland
Address
Garden Hill House
8 Dublin
University College Dublin
Ireland
Address

4 Dublin