Space travel has advanced significantly over the last six decades with astronauts spending up to 6 months at the International Space Station. Nonetheless, the living environment while in outer space is extremely challenging to astronauts. In particular, exposure to space radiation represents a serious potential long‐term threat to the health of astronauts because the amount of radiation exposure accumulates during their time in space. Therefore, health risks associated with exposure to space radiation are an important topic in space travel, and characterizing space radiation in detail is essential for improving the safety of space missions. In the first part of this review, we provide an overview of the space radiation environment and briefly present current and future endeavors that monitor different space radiation environments. We then present research evaluating adverse biological effects caused by exposure to various space radiation environments and how these can be reduced. We especially consider the deleterious effects on cellular DNA and how cells activate DNA repair mechanisms. The latest technologies being developed, e.g., a fluorescent ubiquitination‐based cell cycle indicator, to measure real‐time cell cycle progression and DNA damage caused by exposure to ultraviolet radiation are presented. Progress in examining the combined effects of microgravity and radiation to animals and plants are summarized, and our current understanding of the relationship between psychological stress and radiation is presented. Finally, we provide details about protective agents and the study of organisms that are highly resistant to radiation and how their biological mechanisms may aid developing novel technologies that alleviate biological damage caused by radiation. Future research that furthers our understanding of the effects of space radiation on human health will facilitate risk‐mitigating strategies to enable long‐term space and planetary exploration.

Recently reported studies have led to a heightened awareness of the risks of cancer induced by diagnostic radiological imaging, and in particular, the risk of brain cancer after childhood CT scans. One feature of Ptch1+/– mice is their sensitivity to radiation-induced medulloblastomas (an embryonic cerebellar tumor) during a narrow window of time centered on the days around birth. Little is known about the dynamics of how dose protraction interacts with such narrow windows of sensitivity in individual tissues. Using medulloblastomas from irradiated Ptch1+/– mice with a hybrid C3H × C57BL/6 F1 genetic background, we previously showed that the alleles retained on chromosome 13 (which harbors the Ptch1 gene) reveal two major mechanisms of loss of the wild-type allele. The loss of parental alleles from the telomere extending up to or past the Ptch1 locus by recombination (spontaneous type) accounts for almost all medulloblastomas in nonirradiated mice, while tumors in irradiated mice often exhibited interstit...

The relative biological effectiveness (RBE) of neutrons depends on their physical nature (e.g., energy) and the biological context (e.g., end points, materials). From the perspective of radiological protection, age is an important biological context that influences radiation-related cancer risk, but very few studies have addressed its potential impact on neutron effects. We therefore investigated the influence of age on the effect of accelerator-generated fast neutrons (mean energy, ∼2 MeV) in an animal model of breast carcinogenesis. Female Sprague-Dawley rats at 1, 3 and 7 weeks of age were irradiated with fast neutrons at absorbed doses of 0.0485–0.97 Gy. All animals were kept under specific pathogen-free conditions and screened weekly for mammary tumors by palpation until they were 90 weeks old. Tumors were diagnosed based on histology. Mathematical modeling was used to analyze mammary cancer incidence, collectively using data from this study and a previously reported experiment on 137Cs gamma rays. T...

Although the risk of breast cancer after high-dose-rate irradiation has been firmly established, however, the risk incurred for low-dose-rate irradiation is not well understood. Here we provide experimental evidence for dose rate and age dependencies induced by continuous γ-ray irradiation on mammary carcinogenesis. Female rats received continuous whole-body irradiation at one of the following time points: at 7 weeks of age (denoted adults) at a dose rate of 3−60 mGy/h (4 Gy total); or at either 3 weeks (denoted juveniles) or 7 weeks of age at a dose rate of 6 mGy/h (1−8 Gy total). Additional rats were acutely irradiated at 13 weeks of age at a dose rate of 30 Gy/h (0.5–4 Gy total). We observed the incidence of mammary tumors by weekly palpation until they were 90 weeks old and after pathological inspection upon autopsy. The tumor incidence rate for each group was characterized by Cox regression analysis. When adult rats were irradiated at 60 mGy/h for a total of 4 Gy, their hazard ratio for mammary carci...

Humans are continually exposed to various environmental carcinogens. Cancers may arise as a result of exposure to carcinogenic chemicals, ionizing radiation or a combination thereof. However, the mechanism of combined carcinogenesis has been only deduced from oncogenic actions of individual agents. Here, we analyzed experimental mammary carcinogenesis caused by a combination of radiation and a chemical carcinogen, 1-methyl-1-nitrosourea (MNU). Seven-week-old female Sprague-Dawley rats were divided into 4 groups: control, gγ-irradiated (2 Gy), MNU-treated (40 mg/kg, i.p.) and combined treatment of radiation with subsequent MNU after 3 days. Rats with palpable tumors were sacrificed at 50 weeks of age to collect tumors for histologic typing and mutational analysis of the H-ras gene codon 12. The combined treatment induced adenocarcinomas, but not fibroadenomas, more efficiently than radiation or MNU alone. The H-ras mutation was not seen in radiation-induced carcinomas and was specific to MNU-induced carcinomas in individually treated groups. In the combined treatment group, H-ras-mutated, but not nonmutated, tumors were more frequent and developed significantly earlier than in the MNU-treated group. Significantly higher numbers of cells were stained for activated c-Myc protein in gγ-ray- and combined treatment-induced cancers than in MNU-induced cancers. These results indicate that combined exposure to the 2 carcinogens elicits an unexpected cooperativity in which pre-irradiation enhances mammary carcinogenesis predominantly through the oncogenic pathway involving H-ras, possibly by synergism with c-Myc activation.

Women who are heterozygous for deleterious BRCA1 germline mutations harbor a high risk of hereditary breast cancer. Previous Brca1‐heterozygous animal models do not recapitulate the breast cancer phenotype, and thus all currently used knockout models adopt conditional, mammary‐specific homozygous Brca1 loss or addition of Trp53 deficiency. Herein, we report the creation and characterization of a novel Brca1 mutant rat model harboring the germline L63X mutation, which mimics a founder mutation in Japan, through CRISPR‐Cas9–based genome editing. Homozygotes (Brca1^L63X/L63X) were embryonic lethal, whereas heterozygotes (Brca1^L63X/+) showed apparently normal development. Without carcinogen exposure, heterozygotes developed mammary carcinoma at a comparable incidence rate with their wild‐type (WT) littermates during their lifetime. Intraperitoneal injection of 1‐methyl‐1‐nitrosourea (25 or 50 mg/kg) at 7 weeks of age induced mammary carcinogenesis at comparable levels among the heterozygotes and their littermates. After exposure to ionizing radiation (0.1–2 Gy) at 7 weeks of age, the heterozygotes, but not WT littermates, displayed dose‐dependent mammary carcinogenesis with 0.8 Gy⁻¹ excess in hazard ratio during their middle age; the relative susceptibility of the heterozygotes was more prominent when rats were irradiated at 3 weeks of age. The heterozygotes had tumors with a lower estrogen receptor α immunopositivity and no evidence of somatic mutations of the WT allele. The Brca1^L63X/+ rats thus offer the first single‐mutation, heterozygous model of BRCA1‐associated breast cancer, especially with exposure to a DNA break‐inducing carcinogen. This implies that such carcinogens are causative and a key to breast cancer prevention in individuals who carry high‐risk BRCA1 mutations.