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Background The detrimental health effects associated with the receipt of moderate (0.1–1 Gy) and high (>1 Gy) acute doses of sparsely ionising radiation are well established from human epidemiological studies. There is accumulating direct evidence of excess risk of cancer in a number of populations exposed at lower acute doses or doses received over a protracted period. There is evidence that relative risks are generally higher after radiation exposures in utero or in childhood. Methods and findings We reviewed and summarised evidence from 60 studies of cancer or benign neoplasms following low- or moderate-level exposure in utero or in childhood from medical and environmental sources. In most of the populations studied the exposure was predominantly to sparsely ionising radiation, such as X-rays and gamma-rays. There were significant (p Conclusions Overall, the totality of this large body of data relating to in utero and childhood exposure provides support for the existence of excess cancer and benign neoplasm risk associated with radiation doses

International audience; In 2011, the International Commission on Radiological Protection (ICRP) recommended reducing the occupational equivalent dose limit for the lens of the eye from 150 mSv/year to 20 mSv/year, averaged over five years, with no single year exceeding 50 mSv. With this recommendation, several important assumptions were made, such as lack of dose rate effect, classification of cataracts as a tissue reaction with a dose threshold at 0.5 Gy, and progression of minor opacities into vision-impairing cataracts.However, although new dose thresholds and occupational dose limits have been set for radiation-induced cataract, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological and mechanistic evidence at doses under 2 Gy.Since the release of the 2011 ICRP statement, the Multidisciplinary European Low Dose Initiative (MELODI) supported in April 2019 a scientific workshop that aimed to review epidemiological, clinical and biological evidence for radiation-induced cataracts.The purpose of this article is to present and discuss recent related epidemiological and clinical studies, ophthalmic examination techniques, biological and mechanistic knowledge, and to identify research gaps, towards the implementation of a research strategy for future studies on radiation-induced lens opacities.The authors recommend particularly to study the effect of ionizing radiation on the lens in the context of the wider, systemic effects, including in the retina, brain and other organs, and as such cataract is recommended to be studied as part of larger scale programs focused on multiple radiation health effects.

International audience; The human response to ionizing radiation (IR) varies among individuals. The first evidence of the individual response to IR was reported in the beginning of the 20th century. Considering nearly one century of observations, we here propose three aspects of individual IR response radiosensitivity for early or late adverse tissue events after radiotherapy on normal tissues (non-cancer effects attributable to cell death); radiosusceptibility for IR-induced cancers; and radiodegeneration for non-cancer effects that are often attributable to mechanisms other than cell death (e.g., cataracts and circulatory disease). All the molecular and cellular mechanisms behind IR-induced individual effects are not fully elucidated. However, some specific assays may help their quantification according to the dose and to the genetic status. Accumulated data on individual factors have suggested that the individual IR response cannot be ignored and raises some clinical and societal issues. The individual IR response therefore needs to be taken into account to better evaluate the risks related to IR exposure. © 2016 Elsevier B.V.

Ionizing radiation is a proven human carcinogen and cataractogen. The crystalline lens of the eye is among the most radiosensitive tissues in the body. A clouding of the normally transparent lens (i.e., cataract) is very common. Conversely, the lens continues to grow throughout life without developing tumors, suggesting that the lens possesses strong anti-carcinogenesis mechanisms. There is mounting evidence that mutations of oncogenes, tumor suppressor genes, DNA repair genes involved in base excision repair, nucleotide excision repair, and DNA double-strand break repair, and genes involved in intercellular interactions (e.g., via connexin gap junctions), and inflammation affect cataract development. Associations of these factors with cancer have long been recognized, highlighting that cataractogenesis shares some common mechanisms with carcinogenesis. This paper briefly overviews the current knowledge on the potential involvement of tumor related factors, DNA repair factors, intercellular interactions and inflammation in spontaneous cataractogenesis, and discusses its implications for cataractogenesis induced by targeted and nontargeted effects of ionizing irradiation.

Ionizing radiation-induced genomic instability has been documented in various end points such as chromosomal aberrations and mutations, which arises in the descendants of irradiated mammalian or yeast cells many generations after the initial insult. This study aimed at addressing radiation-induced genomic instability in higher plant tobacco cells. We thus investigated micronucleus (MN) formation and cell proliferation in tobacco cells irradiated with γ-rays and their descendants. In γ-irradiated cells, cell cycle was arrested at G 2 /M phase at around 24 h post-irradiation but released afterward. In contrast, MN frequency peaked at 48 h post-irradiation. Almost half of 40 Gy-irradiated cells had MN at 48 h post-irradiation, but proliferated as actively as sham-irradiated cells up to 120 h post-irradiation. Moreover, the descendants that have undergone at least 22 generations after irradiation still showed a two-fold MN frequency compared to sham-irradiated cells. This is the direct evidence for radiation-induced genomic instability in tobacco cells.

High tolerance against various extreme environments exhibited by some anhydrobionts might be due to being almost completely desiccated, a state where little or no chemical reactions occur. We have shown that anhydrobiotic larvae of Polypedilum vanderplanki have higher tolerance against both high- and low-linear energy transfer (LET) radiation than hydrated larvae. It is of great interest to know how the desiccating larvae gain radiation tolerance. We therefore examined effects of high-LET radiation on four kinds of larvae: (1) normal hydrated (intact) larva, (2) intermediates between the anhydrobiotic and normal hydrated state, (3) almost completely dehydrated (anhydrobiotic) larvae, and (4) immediately rehydrated larvae that are assumed to have a similar molecular profile to anhydrobiotic larvae. The intermediates and immediately rehydrated larvae survived longer after high-LET radiation than intact larvae, indicating that radiation tolerance could be enhanced even in hydrated larvae. Physiological changes toward anhydrobiosis, e.g. accumulation of protectants or increasing damage repair capacity, correlate with improved radiation tolerance in hydrated larvae. In addition, almost complete desiccation further enhanced radiation tolerance, possibly in a different way from the hydrated larvae.

Reticulon (RTN) proteins are localized to the endoplasmic reticulum (ER), and are related to intracellular membrane trafficking, apoptosis, inhibiting axonal regeneration, and Alzheimer's disease. The RTN proteins are produced without an N-terminal signal peptide. Their C-terminal domain contains two long hydrophobic segments. We analyzed the ER localization signal of human RTN1-A. Mutant proteins lacking the first (39 residues) or second (36 residues) hydrophobic segment showed ER localization. On the other hand, the mutant lacking both hydrophobic segments was cytosolic. Enhanced green fluorescent protein (EGFP) tagged with the first or second hydrophobic segment of RTN1-A was localized to the ER. These results suggest that each hydrophobic segment determines the ER localization. In addition, EGFP tagged with the truncated form of the first hydrophobic segment exhibited the localization to the Golgi rather than the ER. This suggests that the length of the hydrophobic segment contributes to the ER retention of RTN1-A.

Recent lines of evidence have indicated that gap junctional intercellular communication (GJIC) participates in cellular response to low-dose ionizing radiation. However, it remains elusive whether GJIC contributes to heat stress response. We demonstrated here a possible link between gap junctions and heat stress response in normal human cells. We found that heat shock at 43 °C transiently augmented the phosphorylation of gap junction protein connexin (Cx) 43, concomitant with GJIC abrogation. We also found that treatment with GJIC inhibitor lindane resulted in the potentiation of hyperthermic killing and attenuated nuclear translocation of heat shock protein 72. These results indicate that GJIC is involved in heat stress response and alleviates heat-induced damage. Our results imply that the dysfunction of GJIC, which is common in tumors, exacerbates hyperthermic lethality.

The biochemical properties of hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) truncated with C-terminal 21 amino acids and expressed in insect cells were analyzed. The enzyme carried copy-back and de novo RNA synthesis activity but not terminal nucleotidyl transferase activity. k(pol) and K(m) for de novo RNA synthesis were calculated as 10.0 pmol/microg/h and 2.5 microM under 0.5 mM GTP and 2.0 pmol/microg/h and 3.5 microM under 50 microM GTP, respectively. Those for copy-back RNA synthesis were similar under both conditions (k(pol), 1.8 pmol/microg/h; K(m), 3.0 microM). De novo RNA synthesis was activated by 0.5 mM GTP. However, the ratio of GTP to three other NTPs was important for activation. Our HCV RdRp showed high activity for the complementary sequence of the HCV internal ribosomal entry site and a synergistic effect of Mg(2+) to Mn(2+).

1. 1. Some parameters for protein synthesis were investigated with the developing ovaries of Bombyx mori. 2. 2. The cell-free translational activities of cytoplasmic RNA fluctuated as expected from the reported patterns for the bulk chorion protein synthesis and fell rapidly at the later period of ovarian development. 3. 3. This fall was not accompanied by changes in content of ribosomes and activity of S-100 enzymes but by a decrease in activity of ribosomes as assayed by a poly(U)-dependent phenylalanine system at a low magnesium ion concentration.

1. 1. The melting temperature of the hybrid of Bombyx ribosomal RNA (rRNA) against Bombyx DNA was compared with that of the hybrid of Antheraea rRNA against Bombyx DNA. 2. 2. The difference of the melting temperature was 4°C. 3. 3. From this finding, the sequential difference between ribosomal gene of Bombyx and that of Antheraea was estimated, and the divergence time of the ribosomal genes between these two species was discussed.