Chronic restraint-induced stress has little modifying effect on radiation hematopoietic toxicity in mice

Abstract

Both radiation and stresses cause detrimental effects on humans. Besides possible health effects resulting directly from radiation exposure, the nuclear plant accident is a cause of social psychological stresses. A recent study showed that chronic restraint-induced stresses (CRIS) attenuated Trp53 functions and increased carcinogenesis susceptibility of Trp53-heterozygous mice to total-body X-irradiation (TBXI), having a big impact on the academic world and a sensational effect on the public, especially the residents living in radioactively contaminated areas. It is important to investigate the possible modification effects from CRIS on radiation-induced health consequences in Trp53 wild-type (Trp53wt) animals. Prior to a carcinogenesis study, effects of TBXI on the hematopoietic system under CRIS were investigated in terms of hematological abnormality in the peripheral blood and residual damage in the bone marrow erythrocytes using a mouse restraint model. Five-week-old male Trp53wt C57BL/6J mice were restrained 6 h per day for 28 consecutive days, and TBXI (4 Gy) was given on the 8th day. Results showed that CRIS alone induced a marked decrease in the red blood cell (RBC) and the white blood cell (WBC) count, while TBXI caused significantly lower counts of RBCs, WBCs and blood platelets, and a lower concentration of hemoglobin regardless of CRIS. CRIS alone did not show any significant effect on erythrocyte proliferation and on induction of micronucleated erythrocytes, whereas TBXI markedly inhibited erythrocyte proliferation and induced a significant increase in the incidences of micronucleated erythrocytes, regardless of CRIS. These findings suggest that CRIS does not have a significant impact on radiation-induced detrimental effects on the hematopoietic system in Trp53wt mice.

Space Radiation Biology for “Living in Space”

“…Using a laboratory mouse model for chronic restraintinduced psychological stress, the pioneering work on concurrent exposure of Trp53 heterozygous C57BL/6 mice to psychological stress and total body γ-rays showed that psychological stress modulates susceptibility to radiation, causing increased susceptibility to radiocarcinogenesis in Trp53-heterozygous mice underlying the mechanism of Trp53 function attenuation [203]. In recent years, studies using the same chronic restraint system, wild-type C57BL/6J male mice aged 5 weeks and total body exposure to 4 Gy X-rays, showed that psychological stress has minimal modifying effects on radiation-induced hematopoietic toxicity and genotoxicity measured as a peripheral blood histogram, MN in the erythrocytes of bone marrow, and splenocyte CAs (insertions, dicentrics, and fragments), suggesting that chronic restraint-induced psychological stress does not appear to synergize with the clastogenicity of low-LET radiation in wild-type animals [204,205]. Interestingly, in the animal model for psychosocial stress using 6-or 8-week-old male ddY mice (model mouse for spontaneous IgA nephropathy) and SAMP10 mice (model mouse for accelerated senescence), results of concurrent exposure to both psychosocial stress and X-rays at a dose of 3-6 Gy showed increased acute damage, namely, reduced 30-day survival, and decreased erythrocyte and leukocyte counts in the peripheral blood and hypocellular bone marrow, indicating psychological stress promotes radiosensitivity of bone marrow in these particular mice [206].…”

Revisiting the health effects of psychological stress—its influence on susceptibility to ionizing radiation: a mini-review

“…Psychological stressors have a major physical component and, similarly, some models of physical stress (such as restraint stress and immobilization stress) can induce PS, at least to some extent (e.g. the chronic restraint model has been used to induce PS [ 24 , 27 ]). As one of the sources of PS, psychosocial stress is also of great concern, and subordinate colony housing has been established as a model in both mice and rats [ 4 , 30 – 32 ].…”

“…In laboratory animal models, studies showed that CRIPS could significantly reduce body weight gain from 1 week after the onset of restraint in rats [ 51 ] and from the day following onset in mice [ 27 ], and promote immune suppression, inducing lymphocyte reduction [ 27 , 52 , 53 ]. In rats exposed to continuous stress from photoperiod, temperature and noise, a significantly increased incidence of micronuclei in peripheral red blood cells (RBCs) was observed [ 54 ].…”

“…In rats exposed to continuous stress from photoperiod, temperature and noise, a significantly increased incidence of micronuclei in peripheral red blood cells (RBCs) was observed [ 54 ]. In mice, it was demonstrated that PS could reduce the RBCs [ 27 ], alter the responsiveness to carcinogens, accelerate tumor onset, promote tumor progression and growth, and alter tumor type and location [ 55 – 58 ].…”

“…Although modulation effects from exposure to PS on radiation-induced health consequences and the mechanisms underlying these outcomes still remain largely unknown, recent studies and our latest investigations in mouse models show that chronic restraint–induced PS (CRIPS) can increase the susceptibility of Trp53-heterozygous mice to radiocarcinogenesis, and cause hematological toxicity in peripheral blood and elevated chromosome aberration (dicentrics) frequency in splenocytes of Trp53– wild-type mice. This has had a big impact on the academic world and a sensational effect on the public [ 24 – 27 ]. This mini-review gives an overview of the significance of PS effects on humans and experimental animals, with a special focus on the context of the importance and perspective for study of the modification effect from PS on radiosusceptibility.…”