Understanding the effects of radiation on health
Content
E ur o p e a n
C o mmi s si o n Communi unity ty Research
Understanding the effects of radiation on health
EURATOM EUR19959
Editors Dr. Ch. Desaintes, Dr. G. Neale Kelly, Ms Karin Coiffard Contact person: Christian Desaintes, EC DG RTD J04 Address: MO75 5/1, 5/1, B-1049 Brussels E-mail: christian.desaintes@cec [email protected] .eu.int
Legal notice Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use which might be made of the following information. A great deal of additional additional information on the European European Union is available on the Internet. It can be accessed through the Europa server (http://europa.eu.int). Luxembourg: Office for Official Publications of the European Communities, 2002 ISBN 92-894-3840 92-894-3840-1 -1 © European Communities, 2002 Reproduction is authorised provided the source is acknowledged. Printed in Belgium
Contents Part 1
4
PREFACE
5
INTRODUCTION
Cellular studies: 14
B. Michael
16
B. Michael
18
A. Natarajan
Part 2
Experimental data for the induction of cancer by radiation of different qualities (EDICAR) Induction, repair and biological consequences of DNA damages caused by radiations of various qualities (RADNA)
Chromatin structure and DNA repair in relation to ionizing ionizi ng radiation-induced chromosome aberration in mammalian cells Factors modifying the yield of radiation-induced chromosome aberrations
20
A. Natarajan
22
L. Mullenders
Mechanisms of formation of ionizing radiation-induced chromosomal aberrations (CHROMOSOME STRUCTURE)
24
L. Mullenders
26
S. Salomaa
28
J. Egozcue
30
L. Sabatier
32
T. Jung
34
A. van der Eb
The molecular basis of DNA damage response and radiosensitivity (DNA DAMAGE RESPONSES) Genomic instability and radiation-induced cancer (RADINSTAB) Role of telomere addition in the stabilisation of radiation-induced DNA breaks Telomere instability and the formation and transmission of radiation induced DNA damage (TELORAD) Evolution of genetic damage in relation to cell cycle control: a molecular analysis of mechanisms relevant for low dose effects The effects of ionising radiation on signal transduction and cell cycle control
Radiation tumorigenesis: mechanisms and pre-disposition: 36
G. Monchaux
38
R. Cox
40
M. Atkinson
42
D. Llyod
44
A. Riches
46
R. Newbold
48
D. Williams
50
G. Thomas
52
G. Thomas
Modelling radiation cancer risk: 54
H. Paretzke
A. Pinchera
58
Ch. Reiners
60
J. Bueren
Part 4
Biophysical models for the induction of cancer by radiation (LOW DOSE RISK MODELS)
Diagnosis/treatment of cancer and radiation injury: 56
Part 3
Risk assessment of exposure to radon decay products (RARAD) The mechanisms and genetics of radiation tumorigenesis (MAGELLANS) Genetic susceptibility to radiation carcinogenesis (GENRAD) Detecting differences in radiation sensitivity of people Molecular mechanisms of radiation carcinogenesis in man Identification and isolation of susceptibility genes involved in radiation-induced cancer in humans (SUS GENES IN RAD CAR) Pathology and molecular biology of thyroid tumours in children and young adults exposed to fallout from the Chernobyl nuclear disaster Chernobyl, an integrated pan-European study: morphology, oncogenes, DNA repair and outcome in radiation carcinogenesis (CHIPS) The newly independent states Chernobyl tumour bank - An international scientific resource (NISCTB)
Part 5
Development of optimal protocols for the diagnosis, treatment, follow-up and preventive measures for post-Chernobyl thyroid carcinoma (NUFISA) (NUFISA)2 2 Improvement of dosimetry for I-131 therapy of lung metastases with special regard to children with thyroid cancer from Belarus following the Chernobyl accident Novel approaches to the treatment of radiation accident patients (NAIMORI)
Non-cancer effects:
Part 6
62
F. Stylianopoulou In utero irradiation of the foetal rodent brain: early effects
64
S. Salomaa
Minisatellite mutations and biodosimetry of population around the Semipalatinsk nuclear test site (SEMIPALATINSK)
Annex 1: projects starting late 2002: 66
P. de Boer
66
L. Mullenders
66
M. Atkinson
Genetic factors predisposing to radiation induction of mutation during early gestation: the role of DNA repair and cell cycle control (GEMRATE) Radiation specific DNA non-double strand break lesions: repair mechanisms and biological effects (NON-DSB-LESIONS)
Genetics of predisposition to radiation-induced cancer of the thyroid t hyroid (GENRAD-T)
66
M. Baumann
Genetic pathways for the prediction of the effects of irradiation European normal and tumour tissue bank (GENEPI-ENTB)
e c a f e r
Ionising radiation is present at low doses and low dose rates in the natural environment, largely from radioactive atoms in minerals formed during the early history of the planet. The technological developments of the 20 th century have resulted in the use of radioactive materials for militar military, y, industrial and medical purposes. The peaceful use of radiation includes power generation, industrial in dustrial testing, bio-medical research, disease diagnosis and cancer therapy – all an integral part of our modern world.
P
These benefits to society need, however, to be weighed against the known potential of radiation to cause health effects in exposed people, principally – tissue injury, cancer and genetic effects that are passed to offspring. Much is known on the likelihood of these health effects effec ts after exposure to radiation at high dos doses es and high dose rates. However, the vast majority of man-made radiation exposures to workers and the general public occur at low doses and low dose rates where risks cannot be reliably assessed by direct observation. obser vation. The majority scientific view is that risks of excess cancer and genetic effects are likely to rise ris e in simple proportion to radiation dose and that even the lowest of doses carries some risk, albeit vanishingly small. However, some suggest that there is a low dose region (the dose threshold) where there is no excess risk of any health effect; conversely, others claim that low dose risks are grossly underestimated. Because of scientific uncertainties, the low dose issue remains an important source of debate in radiation protection and more widely in policy/ standard setting. In order to weigh the socio-economic benefits benefit s of radiation against its potential effects on health, it is essential to gain a better understanding unders tanding of this low dose and low dose rate issue. For this principal reason the European Commission has supported a programme of epidemiological and basic research res earch on the health effects of radiation. This brochure provides an outline of the basic b asic research sponsored by the Commission in its 4th and 5th Framework Programmes. It will be of interest to a relatively broad audience with interests in radiation protection including the safety of nuclearpower generation, medical aspects of radiation exposure, the t he application of new research technologies to environmental issues and new concepts concerning the biological action of radiation. The brochure contains two distinct parts. The first one provides a summary of the Commission supported research in the past decade. The main text of this part may be read at two levels with boxed notes acting to provide simplified explanations of scientifically complex issues and outcomes. The second part includes summaries of many of the projects that make up the relevant research portfolio of the Commission. Epidemiological research is outlined in a separate publication “Epidemiology and retrospective dosimetry” (EUR 19958).
4
C o mmi s si o n Communi unity ty Research
Understanding the effects of radiation on health
EURATOM EUR19959
Editors Dr. Ch. Desaintes, Dr. G. Neale Kelly, Ms Karin Coiffard Contact person: Christian Desaintes, EC DG RTD J04 Address: MO75 5/1, 5/1, B-1049 Brussels E-mail: christian.desaintes@cec [email protected] .eu.int
Legal notice Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use which might be made of the following information. A great deal of additional additional information on the European European Union is available on the Internet. It can be accessed through the Europa server (http://europa.eu.int). Luxembourg: Office for Official Publications of the European Communities, 2002 ISBN 92-894-3840 92-894-3840-1 -1 © European Communities, 2002 Reproduction is authorised provided the source is acknowledged. Printed in Belgium
Contents Part 1
4
PREFACE
5
INTRODUCTION
Cellular studies: 14
B. Michael
16
B. Michael
18
A. Natarajan
Part 2
Experimental data for the induction of cancer by radiation of different qualities (EDICAR) Induction, repair and biological consequences of DNA damages caused by radiations of various qualities (RADNA)
Chromatin structure and DNA repair in relation to ionizing ionizi ng radiation-induced chromosome aberration in mammalian cells Factors modifying the yield of radiation-induced chromosome aberrations
20
A. Natarajan
22
L. Mullenders
Mechanisms of formation of ionizing radiation-induced chromosomal aberrations (CHROMOSOME STRUCTURE)
24
L. Mullenders
26
S. Salomaa
28
J. Egozcue
30
L. Sabatier
32
T. Jung
34
A. van der Eb
The molecular basis of DNA damage response and radiosensitivity (DNA DAMAGE RESPONSES) Genomic instability and radiation-induced cancer (RADINSTAB) Role of telomere addition in the stabilisation of radiation-induced DNA breaks Telomere instability and the formation and transmission of radiation induced DNA damage (TELORAD) Evolution of genetic damage in relation to cell cycle control: a molecular analysis of mechanisms relevant for low dose effects The effects of ionising radiation on signal transduction and cell cycle control
Radiation tumorigenesis: mechanisms and pre-disposition: 36
G. Monchaux
38
R. Cox
40
M. Atkinson
42
D. Llyod
44
A. Riches
46
R. Newbold
48
D. Williams
50
G. Thomas
52
G. Thomas
Modelling radiation cancer risk: 54
H. Paretzke
A. Pinchera
58
Ch. Reiners
60
J. Bueren
Part 4
Biophysical models for the induction of cancer by radiation (LOW DOSE RISK MODELS)
Diagnosis/treatment of cancer and radiation injury: 56
Part 3
Risk assessment of exposure to radon decay products (RARAD) The mechanisms and genetics of radiation tumorigenesis (MAGELLANS) Genetic susceptibility to radiation carcinogenesis (GENRAD) Detecting differences in radiation sensitivity of people Molecular mechanisms of radiation carcinogenesis in man Identification and isolation of susceptibility genes involved in radiation-induced cancer in humans (SUS GENES IN RAD CAR) Pathology and molecular biology of thyroid tumours in children and young adults exposed to fallout from the Chernobyl nuclear disaster Chernobyl, an integrated pan-European study: morphology, oncogenes, DNA repair and outcome in radiation carcinogenesis (CHIPS) The newly independent states Chernobyl tumour bank - An international scientific resource (NISCTB)
Part 5
Development of optimal protocols for the diagnosis, treatment, follow-up and preventive measures for post-Chernobyl thyroid carcinoma (NUFISA) (NUFISA)2 2 Improvement of dosimetry for I-131 therapy of lung metastases with special regard to children with thyroid cancer from Belarus following the Chernobyl accident Novel approaches to the treatment of radiation accident patients (NAIMORI)
Non-cancer effects:
Part 6
62
F. Stylianopoulou In utero irradiation of the foetal rodent brain: early effects
64
S. Salomaa
Minisatellite mutations and biodosimetry of population around the Semipalatinsk nuclear test site (SEMIPALATINSK)
Annex 1: projects starting late 2002: 66
P. de Boer
66
L. Mullenders
66
M. Atkinson
Genetic factors predisposing to radiation induction of mutation during early gestation: the role of DNA repair and cell cycle control (GEMRATE) Radiation specific DNA non-double strand break lesions: repair mechanisms and biological effects (NON-DSB-LESIONS)
Genetics of predisposition to radiation-induced cancer of the thyroid t hyroid (GENRAD-T)
66
M. Baumann
Genetic pathways for the prediction of the effects of irradiation European normal and tumour tissue bank (GENEPI-ENTB)
e c a f e r
Ionising radiation is present at low doses and low dose rates in the natural environment, largely from radioactive atoms in minerals formed during the early history of the planet. The technological developments of the 20 th century have resulted in the use of radioactive materials for militar military, y, industrial and medical purposes. The peaceful use of radiation includes power generation, industrial in dustrial testing, bio-medical research, disease diagnosis and cancer therapy – all an integral part of our modern world.
P
These benefits to society need, however, to be weighed against the known potential of radiation to cause health effects in exposed people, principally – tissue injury, cancer and genetic effects that are passed to offspring. Much is known on the likelihood of these health effects effec ts after exposure to radiation at high dos doses es and high dose rates. However, the vast majority of man-made radiation exposures to workers and the general public occur at low doses and low dose rates where risks cannot be reliably assessed by direct observation. obser vation. The majority scientific view is that risks of excess cancer and genetic effects are likely to rise ris e in simple proportion to radiation dose and that even the lowest of doses carries some risk, albeit vanishingly small. However, some suggest that there is a low dose region (the dose threshold) where there is no excess risk of any health effect; conversely, others claim that low dose risks are grossly underestimated. Because of scientific uncertainties, the low dose issue remains an important source of debate in radiation protection and more widely in policy/ standard setting. In order to weigh the socio-economic benefits benefit s of radiation against its potential effects on health, it is essential to gain a better understanding unders tanding of this low dose and low dose rate issue. For this principal reason the European Commission has supported a programme of epidemiological and basic research res earch on the health effects of radiation. This brochure provides an outline of the basic b asic research sponsored by the Commission in its 4th and 5th Framework Programmes. It will be of interest to a relatively broad audience with interests in radiation protection including the safety of nuclearpower generation, medical aspects of radiation exposure, the t he application of new research technologies to environmental issues and new concepts concerning the biological action of radiation. The brochure contains two distinct parts. The first one provides a summary of the Commission supported research in the past decade. The main text of this part may be read at two levels with boxed notes acting to provide simplified explanations of scientifically complex issues and outcomes. The second part includes summaries of many of the projects that make up the relevant research portfolio of the Commission. Epidemiological research is outlined in a separate publication “Epidemiology and retrospective dosimetry” (EUR 19958).
4
