Katsube Takanori, Wang Bing, Tanaka Kaoru, Ninomiya Yasuharu, Varès Guillaume, Kawagoshi Taiki, Shiomi Naoko, Kubota Yoshihisa, Liu Qiang, Morita Akinori, Nakajima Tetsuo, Nenoi Mitsuru
National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan.
Advanced Medical Instrumentation Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, 904-0495, Japan.
Mutat Res Genet Toxicol Environ Mutagen. 2017 Jan;813:18-26. doi: 10.1016/j.mrgentox.2016.11.005. Epub 2016 Nov 22.
Both ionizing radiation (IR) and psychological stress (PS) cause detrimental effects on humans. A recent study showed that chronic restraint-induced PS (CRIPS) diminished the functions of Trp53 and enhanced radiocarcinogenesis in Trp53-heterozygous (Trp53) mice. These findings had a marked impact on the academic field as well as the general public, particularly among residents living in areas radioactively contaminated by nuclear accidents. In an attempt to elucidate the modifying effects of CRIPS on radiation-induced health consequences in Trp53 wild-type (Trp53) animals, investigations involving multidisciplinary analyses were performed. We herein demonstrated that CRIPS induced changes in the frequency of IR-induced chromosomal aberrations (CAs) in splenocytes. Five-week-old male Trp53 C57BL/6J mice were restrained for 6h per day for 28 consecutive days, and total body irradiation (TBI) at a dose of 4Gy was performed on the 8th day. Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with fluorescence in situ hybridization (FISH) probes for chromosomes 1, 2, and 3. The results obtained showed that CRIPS alone did not induce CAs, while TBI caused significant increases in CAs, mostly translocations. Translocations appeared at a lower frequency in mice exposed to TBI plus CRIPS than in those exposed to TBI alone. No significant differences were observed in the frequencies of the other types of CAs (insertions, dicentrics, and fragments) visualized with FISH between these experimental groups (TBI+CRIPS vs. TBI). These results suggest that CRIPS does not appear to synergize with the clastogenicity of IR.
电离辐射（IR）和心理应激（PS）都会对人类产生有害影响。最近一项研究表明，慢性束缚诱导的心理应激（CRIPS）会削弱Trp53的功能，并增强Trp53杂合子（Trp53）小鼠的辐射致癌作用。这些发现对学术领域以及普通公众都产生了显著影响，尤其是在受核事故放射性污染地区居住的居民中。为了阐明CRIPS对Trp53野生型（Trp53）动物辐射诱导的健康后果的调节作用，进行了涉及多学科分析的研究。我们在此证明，CRIPS会诱导脾细胞中IR诱导的染色体畸变（CA）频率发生变化。将5周龄雄性Trp53 C57BL/6J小鼠连续28天每天束缚6小时，并在第8天进行4Gy的全身照射（TBI）。在28天束缚方案结束时，从脾细胞制备中期染色体铺片，并用针对1号、2号和3号染色体的荧光原位杂交（FISH）探针进行染色。获得的结果表明，单独的CRIPS不会诱导CA，而TBI会导致CA显著增加，主要是易位。与单独接受TBI的小鼠相比，接受TBI加CRIPS的小鼠中易位出现的频率较低。在这些实验组（TBI + CRIPS与TBI）之间，用FISH观察到的其他类型CA（插入、双着丝粒和片段）的频率没有显著差异。这些结果表明，CRIPS似乎不会与IR的致断裂性产生协同作用。
