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Radioactive Contamination and the Health of Women and post-Chernobyl Children -Based on Comparative study of Chernobyl, Seveso and Hiroshima/Nagasaki

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Title: Radioactive Contamination and the Health of Women and post-Chernobyl Children -Based on Comparative study of Chernobyl, Seveso and Hiroshima/Nagasaki


1
Radioactive Contamination and the Health of Women
and post-Chernobyl Children -Based on Comparative
study of Chernobyl, Seveso and Hiroshima/Nagasaki
  • Reiko Watanuki, Yuko Yoshida and Kiyoko Futagami

Chernobyl Health Survey and Healthcare for the
Victims - Japan Womens Network
The 20th anniversary of Chernobyl
Catastrophe International Conference Health
Consequences of the Chernobyl Catastrophe.
Strategy of Recovery 29 May to 2 June 2006,
Kiev
2
Background
  • Our Ecological Philosophy
  • Human being is a part of Nature(eco-system), and
    is not more than a part of Nature
  • Uterus is a smaller eco-system
  • Viewpoint of our research Pollutants and Women
    and childrens health

Chernobyl Health Survey and Health Care for the
Victims Japan Womens Network was established
in 1990. R. Watanuki Director, E-mail
r-watanuki_at_mug.biglobe.ne.jp Y. Yoshida
Secretary, E-mail yosida-y_at_tkd.att.ne.jp , K.
Futagami Vice director
3
Major incidents which affected unborn generations
4
1.2 Health Studies of women and children
  • Reported health conditions among inhabitants in
    contaminated areas.
  • Girls and/or women
  • Thyroid dysfunction, autoimmune disease ,
    disturbance of sexual development, disturbance of
    menstrual function, deteriorated immunity,
    disease of reproductive organs, etc.
  • During pregnancy
  • Pregnancy complications, thyroid disease, anemia,
    urogenital diseases, miscarriage, early
    amenorrhea, premature birth, stillbirth, etc.
  • Fetus
  • Fetal death, insufficient development, hypoxia,
    congenital malformation, etc.
  • Newborns, children and/or adolescents
  • Neonatal death, Unhealthiness, Allergy, Diseases
    of nervous, immune, endocrine and/or reproductive
    systems, etc.

5
2. Emerging science of endocrine disruption
  • T. Colborn et al. discovered an endocrine
    disrupting effect of some chemicals in early
    1990s. (Colborn et al., Our stolen Future, 1996)
  • Endocrine disrupting chemicals (EDCs) are
    chemicals that can disrupt thyroid hormones,
    androgens, estrogens and other endocrine
    processes.
  • In some EDCs, they can act at far below dose than
    previously assumed No Observed Adverse Effect
    Level.
  • Now, EDCs on developing organisms are of greatest
    concern, since the disruptive effects of
    developmental exposure can be irreversible.

6
Concept of developmental basis (origins) of
diseases and endocrine disruption
  • Recently, the focus of developmental toxicology
    has changed to an important and emerging area
    the effect in utero exposures (to some
    environmental agents) that cause permanent
    functional changes, that results in increased
    susceptibility to disease/dysfunction later in
    life span. (Heindel, In the International
    Symposium on Environmental Endocrine Disrupters,
    2003)

7
3. Health condition of post-Chernobyl Children
Our hypothesis, Case of Ms.A
8
  • We hypothesize that in Chernobyl case, for
    example, I131 and Cs137 may have endocrine
    disrupting effect and it may disrupt programs of
    biological response or gene expression or other
    biological homeostasis that may lead
    susceptibility to subsequent exposure to
    environmental agents.
  • Especially exposure to such agents in utero may
    induce more serious effect to developmental
    embryo/fetus. In contaminated area, exposure to
    radiation can continue after birth even they are
    low level. It may lead childrens vulnerability
    which are observed in even today.

Fig. by Watanuki Yoshida
9
Regarding a finding of Endocrine Disrupting
Effect A Japanese distinguished immunologists
Ecological view
  • A comment of Prof T.TADA (Immunologist, Tokyo
    Univ.) (2001)
  • We have considered so far, that separate from
    the outer environment, there was a sort of
    internal environment within a living body, and
    the internal system as microcosm was WORKING
    INDEPENDENTLY from the outer macrocosm, that was
    the organism. Such assumed independent organism
    has been subjected by the medical science. ..

10
A Japanese distinguished immunologists
Ecological view (cont.)
  • However, the issue of Ecology has turned the
    traditional idea upside down, the idea that
    organism is essentially an independent
    existence.
  • Therefore incorporation of environmental
    pollutants, which have endocrine disrupting
    effect, would obviously link the inner organism
    with outer environmental situation. I believe we
    have to look at it as a serious big problem for
    the science of Biology.

11
4. Comparative study Chernobyl vs. Seveso
(Chemical Accident in Italy, 1976)
12
20 years after the accident, Seveso Womens
Health Study started with a new scientific
concept
  • Why we compare Chernobyl with Seveso case?
  • Seveso accident (Chemical -dioxin- exposure
    case)
  • On 10 July 1976, as a result of a chemical
    explosion, residents of Seveso, Italy,
    experienced the highest levels of TCDD (dioxin)
    exposure.
  • Twenty years later(1996), the Seveso Women's
    Health Study (SWHS) was initiated with a new
    scientific concept -Endocrine disrupting effect
    of chemicals.
  • It is a sex-based retrospective cohort study
    of female residents of the most contaminated
    areas, to determine whether the women were at
    higher risk for reproductive disease.

13
Major results
  • Doubling of endometriosis but not significant
    dose response
  • Longer menstrual cycle but only in women exposed
    pre-menarche
  • No increase in spontaneous abortion or birth
    defects (numbers too small)
  • No change in age of menarche
  • Possible small association with birth weight /SGA
  • Increased breast cancer incidence

14
Considerations on SWHS
  • Underestimate of effects possible due to
    potentially high background TEQ
  • Highest exposed women were the youngest at
    follow-up
  • Animal evidence suggests in utero exposure may be
    the more sensitive route for the developing
    fetus.
  • It is possible the effects of TCDD are yet to be
    observed.
  • Continued follow-up of the SWHS cohort and their
    offspring is needed.
  • by B. Eskenazi
  • (in International Symposium on Endocrine
    Disruption 2005, Okinawa, Japan)

15
5. Comparative study Chernobyl vs.
Hiroshima/Nagasaki
  • Victims of Atomic bombs
  • Hiroshima August 6, 1945
  • Died instantaneously or of acute effects of
    radiation exposure about 120,000
  • Nagasaki August 9, 1945
  • Died instantaneously or of acute effects of
    radiation exposure about 75,000
  • Victims include many civilians and children.
    And almost the same number of people could
    survive the acute effects but have faced to fear
    of late effects of irradiation.
  • The number of second generation of survivors
    is thought to be between 300,000 500,000
    (uncertain).

16
5-1. New findings on radiation health effects
after 60 years Increased cancer risk
  • A-bomb survivors epidemiological survey showed
    an elevated incidence of myelodysplastic syndrome
    (MDS) during 1980-2004. MDS was previously called
    as pre-leukemia and is closely related to
    leukemia.
  • It also shows that the elevated incidences of
    solid cancers are still persisting in 1980-2004.
  • At WHO-Nagasaki University joint seminar in
    Geneva September 2005, Prof. M Tomonaga (Nagasaki
    Univ.) presented a hypothesis. He regards that
    A-bomb radiation effect has been lasting for 60
    years.
  • It could be a reasonable hypothesis that the stem
    cells were irradiated and damaged at chromosome
    and eventually DNA by the atomic bomb irradiation
    in 1945 and they are persisting over half
    century, giving rise to cancers.

17
Persistent subclinical inflammation among
survivors was revealed 43-47 years later
  • Neriishi et al. (RERF) revealed the persistent
    subclinical inflammation among survivors at the
    time of 43-47 after exposure. The associations
    with radiation dose were statistically
    significant for some inflammatory indicators.
  • Among inflammatory diseases, associations were
    the strongest for chronic thyroiditis. Such
    associations were seen regardless of the presence
    of clinically detectable inflammatory disorders.
    Authors concluded that the association might
    contribute, as an epigenetic and/or bystander
    effect, to development of several
    radiation-induced disorders (Int. J. Radiat.
    Biol., 2001).

18
5-2. Genetic studies (1948-) by ABCC/RERF
  • Major studies
  • 1.Pregnancy outcomes
  • Major malformations, stillbirth
  • and/or neonatal death (1948-53)
  • (Exposed 31,150, Control 41,066)
  • 2. Sex ratio of children
  • (1948-1962) Total 65,431
  • 3. Chromosome mutations (1967-1987)
  • (Exp. 8,322, Cont. 7,976)
  • 4. Mutations in blood proteins
  • (1975-1988)
  • (Exp. 11,364 Cont. 12,297)
  • Results
  • 1. No statistically demonstrable increase in
    major birth defects.
  • 2. The prediction of the effects of lethal
    mutations on the frequency of male birth is not
    possible.
  • 3. No difference were observed for newly arisen
    mutations.
  • 4. No statistically significance.

19
  • 5. Mortality and cancer incidence (1960- )
  • Children born between
  • 05.1946 12.1984
  • (Both or one of parents
  • exposed 31,150, control 41,066),
  • 6. DNA studies (1996- )
  • 1) Six minisatellite loci
  • Exposed 50 families, 64 children
  • Control 50 families, 60 children
  • 2) Six microsatellite loci
  • 3) DNA from various single-copy genes
  • 7 x 10(6) base pairs
  • 5. To date(2003), no evidence of increased risk.
  • Mortality up to age 20 was not related to
    parental exposure.
  • Additional follow-up is on going.
  • 6.
  • 1)Difference is not statistically significant.
    DNA fingerprints are currently examined.
  • 2) Exposed0,Control0.6
  • Further study is required.
  • 3) No mutation was detected.
  • Extended study is on going.

Exposed (proximally exposed, or parental gonadal
dose0.01Sv by DS86) Control (distally exposed
or not exposed, or gonadal doselt0.01Sv)
20
Major studies on Human DNA minisatellite
1995 Japan No significant difference of mutation rate at minisatellite loci between the exposed and control groups. (A-bomb) Kodaira, Am J Hum. Genet.
1996 Belarus 2 times of mutation rate in children whose parents lived in high contaminated area in Belarus than control. (Residents) Dubrova, Nature
2001 Ukraine No significant difference between the exposed and control groups. However, the mutation rate of children conceived while their fathers were working at Chernobyl site is higher than those conceived at lease 4 months after their fathers had stopped working at the site. (Liquidators) Livshits, Radiation Research.
2002 Ukraine Kazakhstan 1.6-fold increase in mutation rate in the germline of exposed fathers, whereas the maternal germline mutation rate was not elevated. (Residents) Dubrova, Am J Hum. Genet. 1.8 times of the mutation rate in F0 and 1.5 times in F1 generation (Residents near nuclear test site) Dubrova, Science
21
On going genetic studies by RERF and the claims
of children of the survivors against the
Government
  • On going studies
  • DNA studies
  • Mail survey (questionnaires) and clinical studies
    on adult onset type diseases.
  • The claim of children of the survivors (2006)
  • Improvement of A-bomb Survivors Relief law, that
    is, national compensation and its application to
    the second generation.
  • Especially,
  • 1. Include a checkup for cancers into the general
    health examination for the second generations.
  • 2. Perform medical treatments according to the
    result of the health examination
  • 3. Investigate the actual conditions of second
    generations and issue Second generations health
    record book.

22
The movement of children of the survivors
(First organization in Hiroshima was
established in 1973)
1978 Administer of Welfare in Japan stated to start the health examination of children of the survivors. The association Hibaku Nisei opposed it. The association and Administer of Welfare confirmed 5 issues on the examination.
1979 Start of the health examination of children of survivors.
1984 RERF (Radiation Effects Research Foundation) stated to start genetic studies on DNA level. The association objected against it.
1995 A-bomb Survivors Relief Law was approved
1997 Study plans of the genetic effect of the A-bomb radiation (F1 study) was released. (by RERF).
1999 The association and RERF exchanged the note of confirmation about the genetic study.
2001 RERF started F1 Mail survey and clinical study
2006 The association claims against the Government to improve the A-bomb Survivors Relief Law
23
5-3. Osaka District Court in Japan recognized
that diseases of 9 people were caused by Atomic
bomb radiation (12 May 2006)
  • Plaintiffs are between 69 and 81 years old. Seven
    of them were exposed to A-bomb radiation about
    1.5 to 3.3 km from the hypocenters, and the other
    two were exposed to radiation when they entered
    in Hiroshima after the bombing.
  • Later they suffered diseases such as cancers,
    cataract, thyroid hypofunction and etc. The
    Government had rejected to recognize that their
    disease were A-bomb radiation related.

24
  • The judge pointed out that Governments dose
    estimating system is suspected to underestimate
    effects on people exposed further away from the
    hypocenter.
  • Additionally, he said in the ruling it is needed
    to consider health problems caused by residual
    radiation, fallout and internal exposure, which
    has been neglected or very underestimated until
    now.
  • This is an epoch-making ruling because that it
    pointed out the limitation of current dose
    estimation system created and conducted by ABCC
    and RERF.
  • The Government appealed against the decision on
    22 May.

25
5-4. Studies on womens reproductive health by
ABCC
  • Untoward pregnancy outcomes
  • In utero exposure at time of bombing
  • (Exp. 1630)
  • Reproductive functions
  • (1949-57, Hiroshima)
  • Age of menarche
  • (Exposed 1007, Control 993)
  • Untoward pregnancy outcomes (aforesaid)
  • In utero exposure has had significant effects on
    mental and physical growth and development. The
    effect seems particular pronounced for persons
    who were exposed during the period from 8 to 15
    weeks after conception.
  • Reproductive functions
  • Almost same age between exposed group (age 14.71)
    and control group (14.57).

26
  • 2. Amenorrhea immediately after A-bomb exposure
  • (Exposed. 880)
  • 3. Menopause
  • (Exp. 1000, Cont. 950)
  • 4. Fertility
  • (1962-64, Hiroshima/Nagasaki)
  • (Exp. 2400)
  • 2. Observed in half of the mature women. The
    frequency in women with ARS was significant
    higher (69) than women without ARS (33.7).
  • In most (85.5) of the cases, it was
    transient, but about 15 of them continued from
    amenorrhea to menopause.
  • 3. A marked increase in the age groups 40-49. Its
    peak was seen in 1945. It was suggested that
    menopause is definitely accelerated by A-bomb
    exposure, but it cannot be attributed solely to
    direct effect on the ovary.
  • 4. There was no evidence to suggest that those in
    the high radiation dose groups uniformly suffered
    impaired long-range fertility.

27
5-5. Our questions for the A-bomb studies
  • General
  • A-bomb studies were most of single, relatively
    high-dose exposure cases, and they were started 4
    years after exposure. Data in early period is
    unknown or uncertain.
  • The control groups (zero Sv group) include those
    distally exposed or exposed less than 0.01Sv (by
    DS86), and may include those exposed from fall
    out. Exposure from fall out is thought to be
    insignificant dose, but actually, it is
    uncertain.
  • Genetic
  • In the DNA studies, children of exposed group
    were born 10 years after parents exposure. Its
    result cannot be simply compare with the data of
    children whose parents were continuously exposed
    to low level radiation.

28
  • Reproductive health
  • In early study in Nagasaki, it suggested that
    radiation affects not only directly to the fetus
    but also indirectly as a result of its effect on
    the maternal tissue. It was of considerable
    importance in determining the outcomes of these
    pregnancies. However, these considerations were
    not followed by subsequent studies.
  • In pregnancy outcomes study, radiation effects to
    girls of adolescent age are uncertain.
  • In menarcheal age study, about 40 of girls
    remained pre-menarche stage, but follow-up study
    was not found.
  • Very few studies concerning womens reproductive
    health and the study period is short.
    Insufficient follow-up.
  • From our point of view, radiation effect to
    womens reproductive health in Hiroshima/Nagasaki
    data should be re-evaluated.

29
6. New concept of genetic effect of
environmental agents (chemicals and radioactive
substances)
Fig.A Endocrine disruptors
Fig. A shows a contrast of traditional with new
formulations of the interactions of genes and
environment in the determination of phenotype.
(by Myers, In International Seminar on Nuclear
War and Planetary Emergencies, 2003) Fig. B
shows a new mechanism of biological effect of
environment stress through genomic instability.
(by Niwa, Environment and Health, 1998)
Fig.B Radiation effect
30
Health condition of children, who experienced
antenatal exposure in different period after
Chernobyl Accident
  • All subjects were born and are living in
    contaminated areas (1st zone less than 15
    Ci/km2, 2nd zone 15-45 Ci/km2 )
  • Subjects Children at age from 4 to 17, were
    divided into 3 groups.
  • 1st group 105 children born in 1986-87. They
    were in utero at time of the accident
  • 2nd group 100 children born in 1990.
  • 3rd group 96 children born in 1995. Their
    parents were in pubertal period at time of the
    accident
  • Control group 120 children born in 1986-87, 1991
    and 1995

31
  • Peculiarities of each group
  • 1st group Higher incidence of children with
    congenital developmental anomaly, nervous and
    endocrine diseases, and lower physical
    development.
  • 2nd group Higher incidence of children with
    endocrine diseases and lower physical
    development.
  • 3rd group Higher incidence of children with
    psychiatric disorder, congenital developmental
    anomaly, dominant genetic diseases and disbalance
    of physical development. They also have a
    peculiarity having mental retardation and multi
    minor developmental anomalies.
  • (Bondarenko, 2005)

32
Conclusion
  • This sort of situation has significance in
    suggesting problems related to ecological ethical
    norm. The alarm bell given by the soundless
    voices of Chernobyl children has revealed the
    responsibility of our generation.
  • More specifically, it is our responsibility NOT
    to produce, NOT to use or NOT to discharge
    such pollutants that might affect future
    generations eco-system irreversibly, and that
    might cause genetic disorder.
  • In other words, we must seek a society that
    values the principle of non intervention to
    gene as better and preferred option, even it
    means we have to give up some material wealth or
    convenience.

33
  • Therefore, I would like to emphasise that we
    really have to see through the situation of
    Chernobyl children how much we, as current
    generation, are at the risk of forcing unbearable
    suppression to the future generations life and
    health. I believe that it indicates a
    significant challenge human history is facing in
    this 21st century.

34
  • Chernobyl childrens 20 years of radiation
    exposure experience is suggesting that world
    societies should convert its nuclear policy as
    soon as possible.
  • By this conversion, not only nuclear weapons, but
    also technological dependence such as nuclear
    power generation should be reduced. This
    direction is the only way out of suppressing the
    life of future generations.

35
Comments of Japanese distinguished scientists in
the field of radiation effects
  • Prof. M. Tomonaga (Biomedical sciences, Nagasaki
    Univ.) The atomic bomb irradiation-induced
    genetic damage persist over half century and
    probably whole lives of survivors. This finding
    provides discrete evidence that all nuclear
    weapons must be considered more dangerous because
    of emitting radiation and should be abandoned.
    (In WHO-Nagasaki Univ. joint seminar, Geneva,
    Switzerland, 2005)
  • Prof. T. Nomura (Radiation biology and medical
    genetics, Osaka Univ.) My experiments with
    mice anticipated the suggestion that parental
    exposure to radiation and chemicals could induce
    heritable tumors in the next generation. It is
    important to follow all the human subjects
    throughout their lives, especially adult type
    cancer and chronic diseases. (In International
    symposium Transmissible Genetic Risk and Our
    Future, Osaka, Japan, 2005)

36
Acknowledgements
  • Russia Larisa S. Bareva and doctors in
    Children center of antiradiational
    protection (Federal Children Center of
    Antiradiational Protection)
  • Elena B Burlakova (Institute of
    Biochemical Physics RAS)
  • Margarita I Mikhanlenko
    (Chernobyl Global Security Fund)
  • Valentina M Kozeikina (Chernobyl
    Global Security Fund)
  • Belarus Researchers of Institute of Genetics
    and Cytology BAS
  • Olga Alenikova (Childrens Center
    for Oncology and Hematology)
  • Sergey P. Chunikhovskiy (ex-
    Mogilev regional Childrens Hospital)
  • Tamara Kravtsova (Children in
    Trouble in Mogilev)
  • Ukraine Researchers of Institute of Molecular
    Biology and Genetics ASU
  • Angelina I. Nyagu (Association
    Physicians of Chernobyl)
  • Irina G. Ivasenko (Union
    Kiev-Chernobyl)
  • U.K. Late Alice Stewart (ex-Birmingham
    Univ.)
  • Japan Taisei Nomura (Osaka Univ.)
  • Masao Tomonaga (Nagasaki Univ.)
  • Otsura Niwa (Kyoto Univ.)
  • And especially, children of Chernobyl and their
    mothers
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