Small Head Size After in-Utero Exposure to Atomic Radiation

Miller, RobertW.; Blot, WilliamT.

doi:10.1016/s0140-6736(72)92145-9

Cited by 98 publications

(40 citation statements)

References 10 publications

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“…At initial assessment (see Table I), isolated GH-deficient patients had the lowest mean OFC SDS (-I), while there was no significant difference in mean OFC SDS between those who 12 received craniospinal irradiation and those who had cranial irradiation alone. All groups showed a discrepancy between standing height SDS and OFC SDS, where there was relative preservation of head size, most marked in isolated G H deficient patients who had the greatest height deficit and bone age retardation.…”

Section: Resultsmentioning

confidence: 99%

“…The precise mechanisms by which cranial irradiation leads to such intellectual impairment are unknown, and the long-term effect of therapeutic irradiation on skull growth has not been reported, although in utero exposure to atomic radiation is known to result in small head size (12). Thus we have studied head growth with or without GH therapy in the years following cranial irradiation, when the children have become GH deficient, and compared this to the changes of head size in response to GH therapy in patients with isolated GH deficiency.…”

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confidence: 99%

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The Role of Growth Hormone in Stunted Head Growth after Cranial Irradiation

et al. 1987

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

The Role of Growth Hormone in Stunted Head Growth after Cranial Irradiation

et al. 1987

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“…This developmental stage of the cerebral cortex corresponds to 8-9 weeks of human pregnancy (Kameyama, 1983(Kameyama, , 1985. In fact microcephaly and mental retardation were induced by prenatal exposure to the atomic radiation in Hiroshima and Nagasaki with the highest risk in those exposed during 8-15 weeks after fertilization (Miller and Blot, 1972;Miller and Mulvihill, 1976;Schull, 1984, 1993;Otake et al, 1989Otake et al, , 1991Mole, 1990;Yamazaki and Schull, 1990).…”

Section: Brain Mantlementioning

confidence: 99%

“…Studies of the survivors of atomic bombings of Hiroshima and Nagasaki who were exposed to ionizing radiation in utero have demonstrated a significant increase in small head size and mental retardation, with the highest risk in those exposed during 8-15 weeks after fertilization (Miller and Blot, 1972;Miller and Mulvihill, 1976;Schull, 1984, 1993;Otake et al, 1989Otake et al, , 1991Yamazaki and Schull, 1990;Mole, 1990). Schull et al (1992) recently described the findings on magnetic resonance imaging of the brains of five of these mentally retarded survivors.…”

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Radiation‐Induced Apoptosis and Developmental Disturbance of the Brain*

Inouye

1995

Congenital Anomalies

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The developing mammalian brain is highly susceptible to ionizing radiation.A significant increase in small head size and mental retardation has been noted in prenatally exposed survivors of the atomic bombing, with the highest risk in those exposed during 8-15 weeks after fertilization. This stage corresponds to day 13 of pregnancy for mice and day 15 for rats in terms of brain development. The initial damage produced by radiation at this stage is cell death in the ventricular zone (VZ) of the brain mantle, the radiosensitive germinal cell population. During histogenesis of the cerebellum, on the other hand, the external granular layer (EGL) is also radiosensitive. Although extensive cell death results in microcephaly and histological abnormality, both VZ and EGL have an ability to recover from a considerable cell loss and form the normal structure of the central nervous system. The number of cell deaths to induce tissue abnormalities in adult brain rises in the range of 15-25% of the germinal cell population; and the threshold doses are about 0.3 Gy for cerebral defects and 1 Gy for cerebellar anomalies in both mice and rats. A similar threshold level is suggested in human cases in induction of mental retardation.Radiation-induced cell death in the VZ and EGL has been revealed as apoptosis, by the nuclear and cytoplasmic condensation, transglutaminase activation, required macromolecular synthesis, and internucleosomal DNA cleavage. Apoptosis of the germinal cell is assumed to eliminate acquired genetic damage. Once an abnormality in DNA has been induced and fixed in a germinal cell, it would be greatly amplified during future proliferation, bringing with it the risk of producing malformations and tumors. These cells would commit suicide when injured for replacement by healthy cells, rather than undertake DNA repair which is rarely complete. In fact they show very slow repair of cellular damage.Thus the high sensitivity of undifferentiated neural cells to the lethal effect of radiation may constitute a biological defense mechanism.

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“…given from the later stage of major organogenesis to the neonatal period in mice and rats, which roughly corresponds to the 5th to 24th weeks of gestation in the human (Kameyama, 1983), and thereby to the model of the malformation of radiation-induced microcephalia by the human infant (Dekaban, 1968;Plummer, 1952;Miller and Bolt, 1972).…”

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Avoidance Learning Deficits in Prenatally Gamma‐Ray Irradiated Rats

Tamaki

Hoshino

Kameyama

1989

Congenital Anomalies

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Pregnant female rats of the Fischer344 (F344/Du Crj) strain were exposed to gamma-ray radiation of 1.46Gy on day 15 of gestation (vaginal plug = day 0). When male offspring of control and irradiated dams matured, they were trained with various avoidance conditioning paradigms. In the avoidance acquisition paradigm in which one of the tone-on and lights-off signals was presented with predetermined random sequences, the irradiated group had lower overall rates of active avoidance responding than controls. In the go/no-go (active-passive) discrimination avoidance paradigm after rats learned only active avoidance responses to these two different signals, irradiated rats established stable active avoidance rates under the go (tone-on) signal, while they decreased gradually the rate of passive avoidance responding to the no-go (lights-off) signal as the amount of discrimination training increased. In the standard avoidance acquisition paradigm in which only the lights-off signal was used, the irradiated group also was inferior in active avoidance learning to controls. However, the irradiated group showed a high level of anticipatory responding, which was maintained in avoidance conditioning paradigms even though no shock-avoidance contingency was operating. These results indicated that poor associative ability for the warning signal and the shock might result in the active avoidance learning deficits in irradiated rats, and that active responding was more persistent and passive responding declined due to response excitation within a shock paradigm over the subsequent further training.

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Small Head Size After in-Utero Exposure to Atomic Radiation

Cited by 98 publications

References 10 publications

The Role of Growth Hormone in Stunted Head Growth after Cranial Irradiation

The Role of Growth Hormone in Stunted Head Growth after Cranial Irradiation

Radiation‐Induced Apoptosis and Developmental Disturbance of the Brain*

Avoidance Learning Deficits in Prenatally Gamma‐Ray Irradiated Rats

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