Nobuyuki Hamada

Food safety regulations: what we learned from the Fukushima nuclear accident.

On 11 March 2011, the magnitude-9.0 earthquake and a substantial tsunami struck off the northeast coast of Japan. The Fukushima nuclear power plants were inundated and stricken, followed by radionuclide releases outside the crippled reactors. Provisional regulation values for radioactivity in food and drink were set on 17 March and were adopted from the preset index values, except that for radioiodines in water and milk ingested by infants. For radiocesiums, uranium, plutonium and transuranic α emitters, index values were defined in all food and drink not to exceed a committed effective dose of 5 mSv/year. Index values for radioiodines were defined not to exceed a committed equivalent dose to the thyroid of 50 mSv/year, and set in water, milk and some vegetables, but not in other foodstuffs. Index values were calculated as radioactive concentrations of indicator radionuclides ((131)I for radioiodines, (134)Cs and (137)Cs for radiocesiums) by postulating the relative radioactive concentration of coexisting radionuclides (e.g., (132)I, (133)I, (134)I, (135)I and (132)Te for (131)I). Surveys were thence conducted to monitor levels of (131)I, (134)Cs and (137)Cs. Provisional regulation values were exceeded in tap water, raw milk and some vegetables, and restrictions on distribution and consumption began on 21 March. Fish contaminated with radioiodines at levels of concern were then detected, so that the provisional regulation value for radioiodines in seafood adopted from that in vegetables were additionally set on 5 April. Overall, restrictions started within 25 days after the first excess in each food or drink item, and maximum levels were detected in leafy vegetables (54,100 Bq/kg for (131)I, and a total of 82,000 Bq/kg for (134)Cs and (137)Cs). This paper focuses on the logic behind such food safety regulations, and discusses its underlying issues. The outlines of the food monitoring results for 24,685 samples and the enforced restrictions will also be described.

Safety regulations of food and water implemented in the first year following the Fukushima nuclear accident

An earthquake and tsunami of historic proportions caused massive damage across the northeastern coast of Japan on the afternoon of 11 March 2011, and the release of radionuclides from the stricken reactors of the Fukushima nuclear power plant 1 was detected early on the next morning. High levels of radioiodines and radiocesiums were detected in the topsoil and plants on 15 March 2011, so sampling of food and water for monitoring surveys began on 16 March 2011. On 17 March 2011, provisional regulation values for radioiodine, radiocesiums, uranium, plutonium and other transuranic α emitters were set to regulate the safety of radioactively contaminated food and water. On 21 March 2011, the first restrictions on distribution and consumption of contaminated items were ordered. So far, tap water, raw milk, vegetables, mushrooms, fruit, nut, seaweeds, marine invertebrates, coastal fish, freshwater fish, beef, wild animal meat, brown rice, wheat, tea leaves and other foodstuffs had been contaminated above the provisional regulation values. The provisional regulation values for radioiodine were exceeded in samples taken from 16 March 2011 to 21 May 2011, and those for radiocesiums from 18 March 2011 to date. All restrictions were imposed within 318 days after the provisional regulation values were first exceeded for each item. This paper summarizes the policy for the execution of monitoring surveys and restrictions, and the outlines of the monitoring results of 220 411 samples and the enforced restrictions predicated on the information available as of 31 March 2012.

Anhydrobiosis-Associated Nuclear DNA Damage and Repair in the Sleeping Chironomid: Linkage with Radioresistance

Anhydrobiotic chironomid larvae can withstand prolonged complete desiccation as well as other external stresses including ionizing radiation. To understand the cross-tolerance mechanism, we have analyzed the structural changes in the nuclear DNA using transmission electron microscopy and DNA comet assays in relation to anhydrobiosis and radiation. We found that dehydration causes alterations in chromatin structure and a severe fragmentation of nuclear DNA in the cells of the larvae despite successful anhydrobiosis. Furthermore, while the larvae had restored physiological activity within an hour following rehydration, nuclear DNA restoration typically took 72 to 96 h. The DNA fragmentation level and the recovery of DNA integrity in the rehydrated larvae after anhydrobiosis were similar to those of hydrated larvae irradiated with 70 Gy of high-linear energy transfer (LET) ions (4He). In contrast, low-LET radiation (gamma-rays) of the same dose caused less initial damage to the larvae, and DNA was completely repaired within within 24 h. The expression of genes encoding the DNA repair enzymes occurred upon entering anhydrobiosis and exposure to high- and low-LET radiations, indicative of DNA damage that includes double-strand breaks and their subsequent repair. The expression of antioxidant enzymes-coding genes was also elevated in the anhydrobiotic and the gamma-ray-irradiated larvae that probably functions to reduce the negative effect of reactive oxygen species upon exposure to these stresses. Indeed the mature antioxidant proteins accumulated in the dry larvae and the total activity of antioxidants increased by a 3–4 fold in association with anhydrobiosis. We conclude that one of the factors explaining the relationship between radioresistance and the ability to undergo anhydrobiosis in the sleeping chironomid could be an adaptation to desiccation-inflicted nuclear DNA damage. There were also similarities in the molecular response of the larvae to damage caused by desiccation and ionizing radiation.

Emerging issues in radiogenic cataracts and cardiovascular disease

In 2011, the International Commission on Radiological Protection issued a statement on tissue reactions (formerly termed non-stochastic or deterministic effects) to recommend lowering the threshold for cataracts and the occupational equivalent dose limit for the crystalline lens of the eye. Furthermore, this statement was the first to list circulatory disease (cardiovascular and cerebrovascular disease) as a health hazard of radiation exposure and to assign its threshold for the heart and brain. These changes have stimulated various discussions and may have impacts on some radiation workers, such as those in the medical sector. This paper considers emerging issues associated with cataracts and cardiovascular disease. For cataracts, topics dealt with herein include (i) the progressive nature, stochastic nature, target cells and trigger events of lens opacification, (ii) roles of lens protein denaturation, oxidative stress, calcium ions, tumor suppressors and DNA repair factors in cataractogenesis, (iii) dose rate effect, radiation weighting factor, and classification systems for cataracts, and (iv) estimation of the lens dose in clinical settings. Topics for cardiovascular disease include experimental animal models, relevant surrogate markers, latency period, target tissues, and roles of inflammation and cellular senescence. Future research needs are also discussed.

Individual response to ionizing radiation

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.

Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research

The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The 2012 recommendation of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocular lens has now been adopted in the European Union and is under consideration around the rest of the world. However, 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, mechanistic evidence at doses <2Gy. This paper aims to present a review of recently published information on the biological and mechanistic aspects of cataracts induced by exposure to ionizing radiation (IR). The data were compiled by assessing the pertinent literature in several distinct areas which contribute to the understanding of IR induced cataracts, information regarding lens biology and general processes of cataractogenesis. Results from cellular and tissue level studies and animal models, and relevant human studies, were examined. The main focus was the biological effects of low linear energy transfer IR, but dosimetry issues and a number of other confounding factors were also considered. The results of this review clearly highlight a number of gaps in current knowledge. Overall, while there have been a number of recent advances in understanding, it remains unknown exactly how IR exposure contributes to opacification. A fuller understanding of how exposure to relatively low doses of IR promotes induction and/or progression of IR-induced cataracts will have important implications for prevention and treatment of this disease, as well as for the field of radiation protection.

Role of carcinogenesis related mechanisms in cataractogenesis and its implications for ionizing radiation cataractogenesis

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 Irradiation Not Only Inactivates Clonogenic Potential in Primary Normal Human Diploid Lens Epithelial Cells but Also Stimulates Cell Proliferation in a Subset of This Population

Over the past century, ionizing radiation has been known to induce cataracts in the crystalline lens of the eye, but its mechanistic underpinnings remain incompletely understood. This study is the first to report the clonogenic survival of irradiated primary normal human lens epithelial cells and stimulation of its proliferation. Here we used two primary normal human cell strains: HLEC1 lens epithelial cells and WI-38 lung fibroblasts. Both strains were diploid, and a replicative lifespan was shorter in HLEC1 cells. The colony formation assay demonstrated that the clonogenic survival of both strains decreases similarly with increasing doses of X-rays. A difference in the survival between two strains was actually insignificant, although HLEC1 cells had the lower plating efficiency. This indicates that the same dose inactivates the same fraction of clonogenic cells in both strains. Intriguingly, irradiation enlarged the size of clonogenic colonies arising from HLEC1 cells in marked contrast to those from WI-38 cells. Such enhanced proliferation of clonogenic HLEC1 cells was significant at ≥2 Gy, and manifested as increments of ≤2.6 population doublings besides sham-irradiated controls. These results suggest that irradiation of HLEC1 cells not only inactivates clonogenic potential but also stimulates proliferation of surviving uniactivated clonogenic cells. Given that the lens is a closed system, the stimulated proliferation of lens epithelial cells may not be a homeostatic mechanism to compensate for their cell loss, but rather should be regarded as abnormal. This is because these findings are consistent with the early in vivo evidence documenting that irradiation induces excessive proliferation of rabbit lens epithelial cells and that suppression of lens epithelial cell divisions inhibits radiation cataractogenesis in frogs and rats. Thus, our in vitro model will be useful to evaluate the excessive proliferation of primary normal human lens epithelial cells that may underlie radiation cataractogenesis, warranting further investigations.

Cataractogenesis following high-LET radiation exposure

Biological effectiveness of ionizing radiation differs with its linear energy transfer (LET) such that high-LET radiation is more effective for various biological endpoints than low-LET radiation. Human exposure to high-LET radiation occurs in cancer patients, nuclear workers, aviators, astronauts and other space travellers. From the radiation protection viewpoint, the ocular lens is among the most radiosensitive tissues in the body, and cataract (a clouding of the normally transparent lens) is classified as tissue reactions (formerly called nonstochastic or deterministic effects) with a threshold below which no effect would occur. To prevent radiation cataracts, the International Commission on Radiological Protection (ICRP) has recommended an equivalent dose limit for the lens according to the threshold for vision-impairing cataracts. ICRP recommended the threshold of >8Gy in 1984 and an occupational dose limit of 150mSv/year in 1980. These remained unchanged until 2011, when ICRP recommended lowering the threshold to 0.5Gy and the dose limit to 20mSv/year (averaged over 5 years with no single year exceeding 50mSv). Although such reduction of the threshold was based on findings from low-LET radiation, the dose limit was recommended in Sv. Historically, the lens is the exceptional tissue for which ICRP had assigned a special factor in addition to a general radiation weighting factor, predicated on a belief that the lens is more vulnerable to high-LET radiation than other tissues. Considering such radiosensitive nature of the lens, a deeper understanding of a cataractogenic potential of high-LET radiation is indispensable. This review is thus designed to provide an update on the current knowledge as to high-LET radiation cataractogenesis. To this end, changes in ICRP recommendations on lenticular radiation protection, epidemiological and biological findings on high-LET cataractogenesis are reviewed, and future research needs are then discussed.

No evidence for an increase in circulatory disease mortality in astronauts following space radiation exposures.

Previous analysis has shown that astronauts have a significantly lower standardized mortality ratio for circulatory disease mortality compared to the U.S. population, which is consistent with the rigorous selection process and healthy lifestyles of astronauts, and modest space radiation exposures from past space missions. However, a recent report by Delp et al. estimated the proportional mortality ratio for ages of 55-64 y of Apollo lunar mission astronauts to claim a high risk of cardiovascular disease due to space radiation compared to the U.S. population or to non-flight astronauts. In this Commentary we discuss important deficiencies in the methods and assumptions on radiation exposures used by Delp et al. that we judge cast serious doubt on their conclusions.