The Radiation Effects Research Foundation (RERF) is a joint U.S.-Japan research organization responsible for studying the medical effects of radiation and associated diseases in humans for the welfare of the survivors and all humankind. The organization's scientific laboratories are located in Hiroshima and Nagasaki, Japan.RERF's studies into radiation health effects have continued for more than 70 years, making RERF unique for its conduct of epidemiological and other research on such a large population (more than 120,000 individuals) over such a long timeframe. RERF continues its research with the aim of further elucidating the effects of A-bomb radiation on human health.RERF carries out research in numerous scientific fields, including epidemiology, clinical medicine, genetics, and immunology. Findings from RERF's studies are utilized not only for the medical care and welfare of the A-bomb survivors but also for the establishment of international radiation protection standards.
Mammals can now be cloned artificially, but it remains unknown whether they can also maintain their species through cloning. Herein, we continued serial cloning for 20 years from a single donor mouse. These re-cloned mice appeared normal and had normal lifespans, but large structural and lethal mutations accumulated in their DNA with each generation. The birth rate of serial cloning began to decline from the 27th generation, and the 58th generation was the last. When re-cloned mice from near the final generation were mated with males, their oocytes could be fertilized, but most embryos degenerated. However, a few embryos were normalized by meiosis and fertilization and developed to full term, suggesting that mammals rely on sexual rather than asexual reproduction to eliminate genetic anomalies caused by clonal reproduction.
BACKGROUND:We aimed at estimating trends in 5-year net survival for myeloid and lymphoid malignancies, by age group and morphological subtype, using data on patients diagnosed during 2000-2014 and registered by 16 Japanese population-based cancer registries participating in the CONCORD-3 study. METHODS:We analyzed data on adult patients (15-99 years) diagnosed with a myeloid or lymphoid malignancy during 2000-2014 and followed up to December 31, 2014. We estimated 5-year net survival by age group and morphological subtype with the Pohar Perme estimator, and age-standardized the estimates using International Cancer Survival Standard weights. RESULTS:Significant improvements were observed in five-year net survival for myeloid malignancies among patients aged 15-44 years (from 57.3% in 2000-2004 to 72.3% in 2010-2014) and 45-54 years (from 41.9% to 61.3% over the same period). For lymphoid malignancies, 5-year net survival improved for all ages, but the improvement was less pronounced for older patients. Five-year net survival improved by 10% or more for myeloproliferative neoplasms, classic Hodgkin's lymphoma, and follicular lymphoma. Moderate improvement was observed for diffuse B-cell lymphoma and acute myeloid leukemia. CONCLUSIONS:Five-year net survival for patients with hematological malignancies improved throughout 2000-2014 in Japan. The improvement was more pronounced in younger than older patients. Continuous and detailed monitoring of cancer survival trends is crucial for devising effective control strategies for hematological malignancies. [221/250 words].
To assess the biological risks of low-dose/low-dose-rate long-time radiation exposure, we have been conducting the multigenerational accumulation of de-novo mutations. We have succeeded in detecting spontaneous and radiation-induced mutations in the control and exposed mice, respectively, by using the whole-genome sequencing (WGS) technology. We have already identified over 4000 de-novo mutations in a total of 42 offspring mice compared to the original common pair of mice. It took less than 2 years from the first mating of the original pair to the completion of WGS; thus, it is very quick and cost-effective compared to the specific-locus test which is one of the representative risk assessment methods. According to the number of detected mutations, the precision and statistical power to detect de-novo mutations are extremely higher than any conventional risk assessment methods in the mouse model. We have detected a significant increase in the 20 mGy day-1-induced base substitutions, which is the lowest dose rate ever detected in radiation-induced base substitutions. The mouse mutagenesis model based on the WGS technology, therefore, should provide a powerful tool to the risk assessment system, particularly on the low-dose/low-dose-rate long radiation exposures.
Radiation risks for cancer are classified into probabilistic effects because the induction of oncogenic mutations in a single epithelial cell is thought to be causally related to the process of carcinogenesis. However, two observations remain unanswered by the theory. One is a parallel shift of mouse survival curves towards younger ages after a radiation exposure, and the other is a decreasing trend of relative risk for cancer with an increase in postexposure time. Both are readily explained if it is assumed only that a radiation exposure causes a shift of the spontaneous tumours to appear earlier as a result of tissue damage which favours a transformed cell(s) to grow faster. In line with this notion, there are reports showing that exposures to high doses of acute radiation did not increase the proportion of mice dying from tumours, while their lifespans were shortened. In contrast, although there are reports showing a dose-related increase in the proportion of tumour deaths, the studies were either prematurely terminated or the ages were adjusted, and they are not considered to support the tumour induction model of radiation. As it seems that radiation carcinogenesis is a type of tissue response, it should be more appropriately classified as a deterministic effect of radiation. It is added that this article deals mainly with the data obtained under high-dose and high-dose-rate exposure conditions.
Lung cancer is the leading cause of cancer death worldwide. To aid the development of lung cancer control strategies, we analyzed trends in lung cancer survival using data from 16 population-based cancer registries in Japan that participated in the CONCORD-3 study. We included patients aged 15-99 years diagnosed with lung cancer between 2000 and 2014 and followed up until 31 December 2014. A total of 5-year net survival was estimated using the Pohar Perme estimator, stratified by calendar period, age group, sex, histological subtype, and stage. All-ages estimates were standardized with the International Cancer Survival Standard weights. Age-standardized 5-year net survival in 339 277 patients with lung cancer increased slightly over time, from 29.3% (95% confidence intervals 28.1%-30.5%) for patients diagnosed during 2000-2004 to 32.9% (32.3%-33.4%) in 2010-2014. Five-year net survival improved particularly for young patients (15-44 years), for women diagnosed with non-small cell lung cancer and with localized disease. We observed limited or no survival improvement for patients diagnosed with small-cell lung cancer or with distant disease. In Japan, 5-year net survival for patients with lung cancer improved slightly over the 15 years 2000-2014, but no improvement was observed for patients with small-cell lung cancer or with distant disease. Continued surveillance of cancer survival is essential to guide cancer control efforts and further improve treatment outcomes.
