Threshold for radiation-related severe mental retardation in prenatally exposed A-bomb survivors: a re-analysis

Author: Otake M., Schull W.J., Lee S.

Reference: Int. J. Radiat. Biol. — 1996. — Vol.70, № 6. — P. 755–763.

Keywords: 8th-25th week after ovulation, mental effects

Abstract: Significant effects on the developing human brain of exposure to ionizing radiation are seen among individuals exposed in the 8th-25th week after ovulation. These effects, particularly in the highly vulnerable period of 8-15 weeks after ovulation, manifest themselves most dramatically as an increased frequency of severe mental retardation. However, the distribution of cases of severe mental retardation suggests a threshold in the low-dose region. The 95% lower bound of the threshold in those survivors exposed 8-15 weeks after ovulation was zero for the individual data based on the simple linear model, and 0.15 Gy based on the exponential linear model used in our previous report (1987), but the 95% lower bound of the threshold based on all of the data including 21 additional cases with known doses appears to be 0.05 Gy using the maximum likelihood estimates derived from an exponential-linear model. The latter model was selected because it provides the best fit from the standpoint of the stableness and reasonableness of the estimates among the five models applied to the data. When two probably non-radiation-related cases of Down’s syndrome are excluded from the 19 mentally retarded cases exposed 8-15 weeks post ovulation, the 95% lower bound of the threshold is in the range of 0.15-0.25 Gy based on the exponential-linear model used in 1987, but is in the range of 0.06-0.31 Gy when the more reasonable and better model applied here is used. For exposure in the 16-25-week period based on the same model, the 95% lower bound of the threshold changed from 0.25 to 0.28 Gy, both with and without inclusion of the two probable non-radiation-related mentally retarded cases; one of these cases was probably familial in origin since there was a retarded sibling, and the other due to infection, since the individual had Japanese B encephalitis at age 4 years.

URL: http://www.ncbi.nlm.nih.gov/pubmed/8980673

Radiation, retardation and the developing brain: time is the crucial variable

Author: Nowakowski R.S., Hayes N.L.

Reference: Acta Pædiatrica. — 2008. — Vol. 97. — P. 527–531.

Keywords: prenatal exposure, cognitive deficit, brain damages

Abstract: BACKGROUND: Widespread radiation is a threat unique to the modern world. A recent report reveals that sub-clinical damage to human foetuses between 8 and 25 weeks of gestation can result in cognitive deficits still manifest 16-18 years after birth. These previously unrecognised, long-term effects are apparently produced by a relatively short pulse of exposure to radioactive fallout at levels that were previously thought not to be deleterious. This idea is plausible given the nature of the developmental events occurring in the brain during this period of gestation.

CONCLUSION: This exposed population should be examined for other neurological and psychiatric syndromes. If these findings are corroborated, in the event of future radiation exposures, steps should be taken to shield pregnant women who are within this window of vulnerability.

URL: http://www.ncbi.nlm.nih.gov/pubmed/18394093

Neuron loss during early adulthood following prenatal low-dose X-irradiation in the mouse brain

Author: H. Korr, H. Thorsten Rohde, J. Benders et al.

Reference: Int. J. Radiat. Biol. — 2001. — Vol. 77, № 5. — P. 567–580.

Keywords: prenatal low-dose X-irradiation, hippocampal pyramidal cells

Abstract: PURPOSE: Apart from subsequent cell death, little is known about long-term effects of a prenatal low-dose X-irradiation (PLDI) on nuclear (n) and mitochondrial (mt) DNA, and whether these effects are connected with reduced neuron numbers in the adult brain.

MATERIALS AND METHODS: Pregnant mice were X-irradiated with 0, 10 or 50cGy at day 13 (E13) of pregnancy. One day after (E14), or postnatally at day 25 (P25) or P180, the brains of the offspring were analysed concerning the extent of nDNA repair, mt biogenesis, and the relative content of nDNA single strand breaks (SSB). Stereology was applied for evaluating neuronal loss.

RESULTS: One day after irradiation no unrepaired SSB were detected. Significant results were mainly obtained for hippocampal pyramidal cells at P180, particularly cell loss following 50 cGy PLDI, increased SSB content and mt biogenesis (0 vs. 10cGy) but decreased mt biogenesis for 10 vs. 50 cGy.

CONCLUSIONS: A hypothesis closely related to that regarding molecular events during aging is presented for explaining this second wave of cell death in adult mice following PLDI as a result of accumulated mtDNA damage caused by PLDI. A possible relation to the neurodegenerative hypothesis of schizophrenia is discussed.

URL: http://www.ncbi.nlm.nih.gov/pubmed/11382335

Neuro-inflammatory response in rats chronically exposed to (137)Cesium

Author: P. Lestaevel, L. Grandcolas, F. Paquet et al.

Reference: Neurotoxicology. ― 2008. ― Vol. 29, № 2. ― P. 343–348.

Keywords: CNS, Cs137, inflammatory cytokine genes, electrophysiological alterations

Abstract: After the Chernobyl nuclear accident, behavioural disorders and central nervous system diseases were frequently observed in populations living in the areas contaminated by (137)Cs. Until now, these neurological disturbances were not elucidated, but the presence of a neuro-inflammatory response could be one explanation. Rats were exposed for 3 months to drinking water contaminated with (137)Cs at a dose of 400Bqkg(-1), which is similar to that ingested by the population living in contaminated areas in the former USSR countries. Pro-inflammatory and anti-inflammatory cytokine genes were assessed by real-time PCR in the frontal cortex and the hippocampus. At this level of exposure, gene expression of TNF-alpha and IL-6 increased in the hippocampus and gene expression of IL-10 increased in the frontal cortex. Concentration of TNF-alpha, measured by ELISA assays, was also increased in the hippocampus. The central NO-ergic pathway was also studied: iNOS gene expression and cNOS activity were significantly increased in the hippocampus. In conclusion, this study showed for the first time that sub-chronic exposure with post-accidental doses of (137)Cs leads to molecular modifications of pro- and anti-inflammatory cytokines and NO-ergic pathway in the brain. This neuro-inflammatory response could contribute to the electrophysiological and biochemical alterations observed after chronic exposure to (137)Cs.

URL: http://www.ncbi.nlm.nih.gov/pubmed/18295892

Neuroimmune and gene expression changes in chronic fatigue syndrome after the low-dose radiation exposure

Author: D. Bazyka, K. Loganovsky, I. Ilyenko et al.

Reference: 8^th International LOWRAD Conference «The Effects of Low Doses and Very Low Doses of Ionizing Radiation on Human Health and Biotopes», 28–30 September 2009, Rio de Janeiro, Brazil. — P. 117.

Neurobehavioral and cognitive performances of children exposed to low-dose radiation in the Chernobyl accident: The Israeli Chernobyl Health Effects Study

Title: Neurobehavioral and Cognitive Performances of Children Exposed to Low-Dose Radiation in the Chernobyl Accident -The Israeli Chernobyl Health Effects Study

Author: N. Bar Joseph, D. Reisfeld, E. Tirosh, Z. Silman and G. Rennert

Reference: Am. J. Epidemiol. (2004) 160 (5): 453-459

doi: 10.1093/aje/kwh231

Keywords: accidents, radiation; child; cognition; health; neurobehavioral manifestations; radiation

Abstract: Exposure to low levels of ionizing radiation after the Chernobyl accident in the Ukraine could potentially have influenced the neurobehavioral and cognitive performances of exposed children. A cohort study of adolescents who were children at the time of the accident and who subsequently emigrated to Israel was conducted in 1998–2001. A total of 1,629 children (59% of all 2,769 invited) were included in the study (41% from higher contamination areas, 25% from lower contamination areas, 34% from noncontaminated areas). Mean scores of the Raven Standard Progressive Matrices Test were highest in children in all exposure groups whose parents had a high level of education. No overall relation was found between the cognitive function scores of the child and his/her putative radiation exposure level. Conners’ test T scores did not differ significantly by level of exposure. Mothers of all exposure groups who were pregnant at the time of the accident gave their children significantly higher Conners’ test scores than did those who were not pregnant. Scores for hyperactivity and attention-deficit/hyperactivity disorder were significantly higher among those who were in utero at the time of the accident. These results do not show differences of neurobehavioral or cognitive performance in exposed versus nonexposed children. There is a possible behavioral effect among offspring of pregnant mothers or mothers of very young children in all exposure levels.

URL: http://aje.oxfordjournals.org/content/160/5/453.long

Mortality from diseases other than cancer following low doses of ionizing radiation: results from the 15-Country Study of nuclear industry workers

Author: M. Vrijheid, E. Cardis, P. Ashmore et al.

Reference: Int. J. Epidemiol. — 2007. — Vol. 36, № 5. — P. 1126–1135.

Keywords: nuclear workers, 15 countries, socioeconomic status, non-cancer disease

Abstract: BACKGROUND: Ionizing radiation at very high (radio-therapeutic) dose levels can cause diseases other than cancer, particularly heart diseases. There is increasing evidence that doses of the order of a few sievert (Sv) may also increase the risk of non-cancer diseases. It is not known, however, whether such effects also occur following the lower doses and dose rates of public health concern.

METHODS: We used data from an international (15-country) nuclear workers cohort study to evaluate whether mortality from diseases other than cancer is related to low doses of external ionizing radiation. Analyses included 275 312 workers with adequate information on socioeconomic status, over 4 million person-years of follow-up and an average cumulative radiation dose of 20.7 mSv; 11 255 workers had died of non-cancer diseases.

RESULTS: The excess relative risk (ERR) per Sv was 0.24 [95% CI (confidence intervals) -0.23, 0.78] for mortality from all non-cancer diseases and 0.09 (95% CI -0.43, 0.70) for circulatory diseases. Higher risk estimates were observed for mortality from respiratory and digestive diseases, but confidence intervals included zero. Increased risks were observed among the younger workers (attained age

CONCLUSIONS: The most informative low-dose radiation study to date provides little evidence for a relationship between mortality from non-malignant diseases and radiation dose. However, we cannot rule out risks per unit dose of the same order of magnitude as found in studies at higher doses. (full text available on web)

URL: http://ije.oxfordjournals.org/content/36/5/1126.long

Mortality from cardiovascular diseases among male workers at the radiochemical plant of the “Mayak” complex

Author: M.G. Bolotnikova, N.A. Koshurnikova, N.S. Komlevaet al.

Reference: Sci. Total. Environ. — 1994. — 142: — 29–31.

Keywords: cardiovascular disease, ischemic heart disease, cerebrovascular disease

Abstract: An epidemiologic retrospective study was conducted on the basis of a personnel registry, including 9373 male workers who had started to work at the radiochemical plant during the period from 1948 to 1972, inclusive. Male mortality from cardiovascular disease proved to be 271.1 cases in 100,000 persons/year on average. The age-standardized mortality amounted to 502.5 cases in 100,000 persons/year, which is significantly lower than that of the entire male population. Regarding the structure of mortality from cardiovascular diseases in the studied male groups, the mortality rate from ischemic heart disease (IHD) was 63.7% and that from cerebrovascular disease 21.5%, compared with 57% and 30%, respectively, for the general male population. Mortality from cardiovascular diseases is lower in the study groups than in the general public and does not depend on the external gamma-irradiation dose.

URL: http://www.ncbi.nlm.nih.gov/pubmed/8178133

Radiation injury and neurogenesis

Author: Monje M.L. Palmer T.

Reference : Curr. Opin. Neurol. ― 2003. ― Vol. 16, № 2. ― P. 129–134.

Keywords: vasculopathy, CNS, hippocampal formation, cranium

Abstract: PURPOSE OF REVIEW: For many cancers, survival depends on aggressive combined therapies, but treatment comes at a price. Children and adults who receive radiotherapy involving the brain frequently experience a progressive cognitive decline. The overt pathologies of radiation injury such as white matter necrosis or vasculopathy are the obvious “smoking guns” of dysfunction. However, many patients exhibit severe learning and memory deficits with no overt pathologic changes. This is especially true when the radiation field involves the temporal lobes. The cause of this debilitating dysfunction is currently unknown and untreatable.

RECENT FINDINGS: Within the temporal lobe, the hippocampal formation plays a central role in short-term learning and memory–the functions most notably affected by radiation. Recent work has also shown that hippocampus-dependent learning and memory are strongly influenced by the activity of neural stem cells and their proliferative progeny. The hippocampal granule cell layer undergoes continuous renewal and restructuring by the addition of new neurons. Radiation at much lower doses than that needed to injure the more resistant post-mitotic neurons and glia of the brain has been found to affect these highly proliferative progenitors severely. The stem/progenitor cell is so sensitive to radiation that a single low dose to the cranium of a mature rat is sufficient to ablate hippocampal neurogenesis.

SUMMARY: Progressive learning and memory deficits following irradiation may be caused by the accumulating hippocampal dysfunction that results from a long-term absence of normal stem/progenitor activity. Here, the authors describe the nature of this stem cell dysfunction and contemplate how restoration of stem/progenitor cell activity might be approached in experimental models and, eventually, the clinic.

URL: http://www.ncbi.nlm.nih.gov/pubmed/12644738

Psychological effects of nuclear warfare

Author: Mickley G.A.

Reference:  Military radiobiology / J.J. Conklin, R.I. Walker (Eds.). ― San-Diego: Academic Press, Inc., 1987. ― P. 303–319.

Abstract: Describes psychological aspects of injuries of wars. In all
wars, a certain portion of injuries are related to psychology. Full text available on web.

URL: http://books.google.co.jp/books?id=q_JEJrG-Gq8C&pg=PA303&lpg=PA303&dq=Psychological+effects+of+nuclear+warfare+mickley&source=bl&ots=EgcZNezYJk&sig=kD3Qr1qm7a8yW5b_WOk8FhN0TH0&hl=ja&sa=X&ei=RSTzUemjAs3hkAWy-4CYBw&ved=0CDgQ6AEwAg#v=onepage&q=Psychological%20effects%20of%20nuclear%20warfare%20mickley&f=false