**1. Introduction**

Human spaceflight and exploration began in the 1960s. Manned spaceflight activities have continually expanded in frequency and scope since that time, and plans are now forming for long-duration flights to deep-space destinations. However, numerous risk factors have potential to negatively affect the astronauts' health during deep-space missions, especially microgravity and space radiation. Exposure of astronauts to space radiation is relatively unpredictable yet inevitable. Space radiation comes from two major sources: solar particle events (SPE) emanating from the sun and galactic cosmic rays (GCR) originating from sources outside the solar system.

SPE mainly includes protons and can lead to moderate- to high-dose rate exposures to ionizing radiation during long-term space mission [1, 2]. Astronauts may receive cumulative doses from 1 to 3 gray (Gy) during an SPE [3, 4]. Especially, proton radiation contributes to more than 80% of SPE [1, 2, 5].

GCR contains high atomic number and energy (HZE) particles, such as 56Fe, 28Si, 16O, 12C, and so forth. HZE particles are characterized by dense tracks of ionization, a property quantified as high-linear energy transfer (LET). The properties of HZE particles are consistent with their stronger toxicities and higher energy to normal tissues than photon and proton radiation [6, 7]. Previous studies have documented that the value of RBE in relation to γ-ray radiation was 1.25 for 56Fe, 1.4 for 28Si, and 0.99 for 12C using a mouse model [6, 8]. Among HZE particles, 56Fe has

high-linear energy transfer that might heavily contribute to GCR in space [9]. There are many different components including ions, hydrogen, helium, and so on in spacecraft [10]. Based on measurements in the Mars Science Laboratory from 2011 to 2012, the irradiation dose of GCR in the spaceflight was approximately 481 ± 80 μGy per day [11]. For a 600- to 900-day Mars mission, the total radiation doses from GCR reside between 0.33 and 0.49 Gy. Therefore, the total radiation dose from SPE and GCR will reach to 1.0 Gy or above. Although doses and dose rates of space radiation are low, it will still result in space dose accumulation in the body and high risk to astronauts' health during a long-term space mission [9, 12].

Radiation-induced tissue damage in the body has long been understood since Wilhelm Röntgen discovered X-ray in 1895 [13]. Hematopoietic and gastrointestinal systems have been shown to be the two most sensitive compartments of the body to radiation. It has been well-documented that radiation (including space radiation) also induces dysfunction of the brain, manifesting as behavioral and cognitive disabilities [14, 15]. The detrimental effects of X-ray radiation in the body were firstly reported by Warren and Whipple [16] and Shouse et al. [13]. They reported that exposing dogs to high doses of X-rays resulted in death from severe hematopoietic suppression and damage. The detrimental effects of radiation on human health were heavily realized after the use of the first atomic bombs in 1945. Many people in Hiroshima and Nagasaki who survived the initial bomb blast later died from radiation exposure in the event. Long-term toxic impacts of the atomic bomb on humans were observed as well, such as the high risk of hematopoietic malignancies. Further studies proved that hematopoietic failure was one of the primary reasons in radiation-induced death when animals experienced a moderate to high dose of total-body irradiation. This is supported by a study in the 1940s showing that shielding the spleen or one entire hind leg with lead or transplantation of splenocytes protected mice from the lethal effect of irradiation [17]. The importance of hematopoietic cells under radiation was also supported by studies showing that intravenous infusions of bone marrow (BM) cell suspensions protected mice from the effects of radiation [95]. Initially, investigators suggested that a humoral factor from the spleen and BM cell suspensions might benefit the radioprotective effects [18], while later studies proved that it was attributed to the transplanted hematopoietic cells [19–21]. When Till and McCulloch discovered hematopoietic stem cells (HSCs) in the 1960s, those cells protecting animals from IR-induced lethal hematopoietic damage were HSCs [22, 23]. Remarkable progress has been subsequently made in understanding of the mechanisms by which radiation causes hematopoietic damage.

However, the effects of space radiation on the hematopoietic system have yet to be fully understood, leading to a lack of effective countermeasure strategies thus far. In the present chapter, we mainly focus our discussion on the biological effectiveness of space radiation, such as proton and oxygen, whereby space radiation induces HSC injury, and the implication of HSC injury to IR-induced BM suppression in mouse. In addition, genomic instability, malignancies, and intestinal, brain, behavioral, and cognitive effects induced by space radiation will not be discussed here, which were extensively discussed by other investigators [24, 25].
