Enhanced Effects of Chronic Restraint-Induced Psychological Stress on Total Body Fe-Irradiation-Induced Hematopoietic Toxicity in <i>Trp53</i>-Heterozygous Mice

Abstract

Humans are exposed to both psychological stress (PS) and radiation in some scenarios such as manned deep-space missions. It is of great concern to verify possible enhanced deleterious effects from such concurrent exposure. Pioneer studies showed that chronic restraint-induced PS (CRIPS) could attenuate Trp53 functions and increase gamma-ray-induced carcinogenesis in Trp53-heterozygous mice while CRIPS did not significantly modify the effects on X-ray-induced hematopoietic toxicity in Trp53 wild-type mice. As high-linear energy transfer (LET) radiation is the most important component of space radiation in causing biological effects, we further investigated the effects of CRIPS on high-LET iron-particle radiation (Fe)-induced hematopoietic toxicity in Trp53-heterozygous mice. The results showed that CRIPS alone could hardly induce significant alteration in hematological parameters (peripheral hemogram and micronucleated erythrocytes in bone marrow) while concurrent exposure caused elevated genotoxicity measured as micronucleus incidence in erythrocytes. Particularly, exposure to either CRISP or Fe-particle radiation at a low dose (0.1 Gy) did not induce a marked increase in the micronucleus incidence; however, concurrent exposure caused a significantly higher increase in the micronucleus incidence. These findings indicated that CRIPS could enhance the deleterious effects of high-LET radiation, particularly at a low dose, on the hematopoietic toxicity in Trp53-heterozygous mice.

Keywords

• chronic restraint-induced stress
• total-body irradiation
• iron-particle radiation
• peripheral blood hemogram
• bone marrow micronucleated erythrocytes
• mouse restraint model