Cell death in the developing rat cerebellum following X-irradiation of 3 to 100 rad: A quantitative study.

Inouye, Minoru; Kameyama, Yoshiro

doi:10.1269/jrr.24.259

Cited by 31 publications

(18 citation statements)

References 12 publications

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“…These cells keep similar levels of radiosensitivity until the EGL declines ( Fig. 2) (Inouye and Kameyama, 1983).…”

Section: Cerebellummentioning

confidence: 93%

“…When undifferentiated cell populations of both the VZ of the cerebral mantle and the EGL of the cerebellum are exposed to X-rays in the low dose-range, cell mortality increases linearly with increasing doses (Fig. 2) (Inouye and Kameyama, 1983;Hoshino and Kameyama, 1988). Even a very low dose of 0.03 Gy can induce a statistically significant increase of cell mortality in the EGL of rat cerebellum (Table 1) (Inouye and Kameyama, 1983).…”

Section: Dose-effects On Cell Mortalitymentioning

confidence: 99%

“…During the second phase of development, from the first to the third weeks after birth in rodents, the germinal cells of the external granular layer (EGL), which occupy the surface of the primordial cerebellum, actively proliferate and produce these neurons; this contributes to the formation of the cerebellar cortex. The cells of the EGL are particularly sensitive to ionizing radiation and are readily killed (Inouye and Kameyama, 1983;Inouye et al, 1992aInouye et al, , 1992bInouye et al, , 1992cFerrer et al, 1993a). These cells keep similar levels of radiosensitivity until the EGL declines ( Fig.…”

Section: Cerebellummentioning

confidence: 99%

“…Even a very low dose of 0.03 Gy can induce a statistically significant increase of cell mortality in the EGL of rat cerebellum (Table 1) (Inouye and Kameyama, 1983). M a y , y = 21x+0.22; M a y , y = 1 8~4 .…”

Section: Dose-effects On Cell Mortalitymentioning

confidence: 99%

“…M a y , y = 21x+0.22; M a y , y = 1 8~4 . 0 3 ; 134ay, y = 2 2 x 4 1 1 ; (Inouye and Kameyama, 1983).…”

Section: Dose-effects On Cell Mortalityunclassified

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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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“…These cells keep similar levels of radiosensitivity until the EGL declines ( Fig. 2) (Inouye and Kameyama, 1983).…”

Section: Cerebellummentioning

confidence: 93%

Section: Dose-effects On Cell Mortalitymentioning

confidence: 99%

Section: Cerebellummentioning

confidence: 99%

Section: Dose-effects On Cell Mortalitymentioning

confidence: 99%

“…M a y , y = 21x+0.22; M a y , y = 1 8~4 . 0 3 ; 134ay, y = 2 2 x 4 1 1 ; (Inouye and Kameyama, 1983).…”

Section: Dose-effects On Cell Mortalityunclassified

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Radiation‐Induced Apoptosis and Developmental Disturbance of the Brain*

Inouye

1995

Congenital Anomalies

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Developmental‐stage‐dependent radiosensitivity of neural cells in the ventricular zone of telencephalon in mouse and rat fetuses

Hoshino

Kameyama

1988

Teratology

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Pregnant ICR mice were treated with single whole-body X-radiation at a dose of 0.24 Gy on day 10, 13, or 15 of gestation. Fetuses were obtained from mothers during 1 and 24 hours after irradiation. Pyknotic cells in the ventricular zone of telencephalon were counted in serial histological sections. Incidence of pyknotic cells peaked during 6 and 9 hours after irradiation in each gestation day group. Then, dose-response curves were obtained 6 hours after 0-0.48 Gy of irradiation. All three dose-response curves showed clear linearity in the dose range lower than 0.24 Gy. Ratios of radiosensitivity estimated from the slopes of dose-response curves in day 10, 13, and 15 groups were 1, 1.4, and 0.4, respectively. These demonstrated that ventricular cells in the day 13 fetal telencephalon were the most radiosensitive among the three different age groups. In order to confirm the presence of the highly radiosensitive stage common to mammalian cerebral cortical histogenesis, pregnant F344 rats were treated with single whole-body gamma-irradiation at a dose of 0.48 Gy on day 13, 14, 15, 17, or 19 of gestation. The incidence of pyknotic cells in the ventricular zone of telencephalon was examined microscopically during 1 and 24 hours after irradiation. The peak incidence was shown 6 hours after irradiation in all the treated groups, and the highest peak incidence was shown in day-15-treated group. The developmental stage of telencephalon of day 15 rat fetuses was comparable to that of day 13 mouse fetuses. Thus, the highest radiosensitivity in terms of acute cell death was shown in the same developmental stage of brain development, i.e., the beginning phase of cerebral cortical histogenesis, in both mice and rats.

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Effects of Prenatal Irradiation on Postnatal Psychophysiological Development

Jensh

1986

Handbook of Behavioral Teratology

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Cell death in the developing rat cerebellum following X-irradiation of 3 to 100 rad: A quantitative study.

Cited by 31 publications

References 12 publications

Radiation‐Induced Apoptosis and Developmental Disturbance of the Brain*

Radiation‐Induced Apoptosis and Developmental Disturbance of the Brain*

Developmental‐stage‐dependent radiosensitivity of neural cells in the ventricular zone of telencephalon in mouse and rat fetuses

Effects of Prenatal Irradiation on Postnatal Psychophysiological Development

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