الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Radiation is the emission of energy from a source and its absorption by an object. It is classified according to its interaction with normal chemical matter into ionizing and non-ionizing radiation. The spectrum of non-ionizing radiation is divided into two major categories: the electromagnetic fields and the optical radiations. Electromagnetic fields comprise microwaves and the very high and very low radio waves whereas the optical radiations are sub-divided into UV, visible and infra-red rays. The spectrum of ionizing rays is divided into particulate radiation in the form of alpha, beta and neutronin addition to non-particulate radiation in the form of X- and -rays.
Non-ionizing radiations exert biological effectson human health because of either thermal damage or photochemical damagewhich can provoke biochemical or behavioral changes tothe organism or selectively to certain radiosensitive tissues or cell populations. Damage caused by optical radiations is limited to the eye and skinalthoughmedically applied in several applications such asthe neonatal phototherapy as well asthe surgical and therapeutic lasers and physiotherapy.
The ionizing radiation can induce direct or indirect ionization due to its quantum energy that exceeds the ionizing potential of absorber’s atoms and molecules. Similarly, it has several practical applications in industry, agriculture and medicine. It is frequently used on a daily basis in hospitals and clinics to perform diagnostic imaging and radiotherapy. However, it can also pose a health hazard in case of improper use.
Certain subsets of T lymphocytes emerge from a common and naïve precursor as a result of the signaling events involved in their lineage-specific differentiation. The production of IL-12 by DCs and macrophages helps in the differentiation of activated naïve CD4+ T cells (Th0 cells) into Th1 cells. IL-12 and its related family of cytokines are important for the development of protective innate and adaptive responses to many intracellular pathogens. On the other hand, the differentiation of naïve CD4+ T cell precursors into Th2 cells is enhanced by IL-4 produced by DCs and other innate cell populations. The principal factor determining the development of lineage-specific differentiation is the type of antigens that initiate DC response. For example, IL-12 is produced following activation of DCs, macrophages and NK cells by intracellular bacteria and viruses under the control of a complex cell signaling and transcriptional events. IL-12 up-regulates IFN- via STAT4, leading to IFN--mediated STAT1 activation and induction of the Th1 lineage-determining transcription factor T-bet. In contrast, IL-4 is released by the activation of mast cells by the antigens of parasite worms due totheir ability to activate STAT6, resulting in the induction of the transcription factor GATA3 that results in the signature cytokine profile associated with the Th2 lineage.
The ionizing and non-ionizing radiations could shift the balance of Th1/Th2 cell response; an effect that is closely associated with the reduction of Th1 cytokine mRNA expression and the increase in the mRNA levels of the Th2-type cytokines. This altered Th1/Th2 balance is attributed to the modulation of cytokine-mediated transcriptional factors and signaling pathways. Hence, enhanced Th2 response may mediate immune suppression and reduce the cell-mediated immunity.
Accumulating evidence demonstrated the variability in the responsiveness of different immunologic cell populations to non-ionizing versus ionizing radiations and to low doses versus high doses. The impact of high dose radiation on suppressing the immune system has been demonstrated and confirmed both experimentally and in epidemiological studies. However, the effects of low dose ionizing radiation on the immune system are largely contradictory.Earlier observations indicate that chronic low dose irradiation could cause immune suppression which is maintained through several mechanisms.However, a substantial body of evidence described immune stimulatory effectsfor low dose radiation on various aspects of cell-mediated and humoral immunity. Studies focusing on the effect of different durations of recovery on orienting the immune modulation induced by radiation exposure (in particular, cell proliferation and Th1/Th2 cytokine balance) are relatively mediocre. Furthermore,elucidationof the influence of functional responsiveness of immunologic cell pools to different forms of irradiation(direct exposure of splenocyte suspensions or intact spleens versus whole body irradiation) is needed.
The present study was conducted on a total of 187 male C57Bl/6J mice exposed as a whole body to UVB (1 hour, 49 mice), low dose (0.2 gray, 21 mice) and variable high doses of radiation (5, 10, and 20 gray, 105 mice while the control group comprised 12 mice). Mice were tested for the effect of recovery time after irradiation (1 day, 3 days and 7 days) on study parameters. In addition, intact spleens and pools of isolated splenocyte suspensions were exposed to the same conditions of irradiation. The functional activities of splenocyte cell populations and their radiation-influenced cytokine profile were investigated. The adaptive cellular immune response and the functional interplay between Th1 and Th2 subpopulations were monitored by in vitro assessment of the lymphoproliferative responsiveness to T and B cell-specific mitogens (Con A and PWM respectively) as well as by measurement of the basal and mitogen-stimulated IL-12 and IL-10 release following short-term culture of these splenic cell populations.
Splenocyte suspensions were individually prepared by simple squeezing and subsequently employed in tissue culture assays. Splenocytes were tested for viability by Trypan blue dye exclusion test and counted before assessment. The lymphocyte proliferation was assessed by MTT assay using two different types of plant lectins as mitogens; Con A and PWM. IL-10 and IL-12 cytokines were measured by ELISA. The data were analyzed by SPSS and results were considered statistically significant at P< 0.05.
The results obtained in the present study revealed that in vitro exposure of splenocyte suspensions to UVB radiation did not show remarkable effects on basal or mitogen-induced IL-10 between 30 min and 1 hour recovery durations while only Con A-induced IL-12 was more elevated and only spontaneous proliferation was reduced at the same level of comparison. Regarding intact spleens exposed to UVB radiation, they did not show significant changes neither in IL-10 nor in IL-12 expression while significant decrease in spontaneous and mitogen-induced proliferation was obtained.
The results obtained in the present study indicated that mice exposed as whole bodies to UVB exhibited suppressed lymphoproliferative response either spontaneously or after mitogen stimulation in comparison to un-exposed animals; and that there is a remarkable tendency to recover by time although still below normal levels even 7 days later. Concerning IL-12 release, similar results were obtained except that results recorded after 7 days exceeded significantly that of the control levels. Regarding IL-10, the data revealed a significant suppression followed by a similar time-dependent recovery that was broken at the 7-day duration coinciding with the peak IL-12. These results indicate that whole body exposure to UVB caused an immediate state of suppression expressed as reduced cell proliferation and IL-10 and IL-12 cytokine release, and that there was a remarkably gradual tendency to recover by time –in particular- at 7 days.
In the present study, exposure of splenocyte suspensions to varying high doses of radiation caused a state of conventional immune suppression that is characterized by being dose-dependent and is manifested by decreased cell proliferation and IL-12 release accompanied by increased IL-10 production. On the other hand, exposure of intact spleens to the same doses of radiation caused spontaneous and dose-dependent immune stimulation manifested by enhanced cell proliferation and elevated IL-12 production with decreased IL-10 release.
Exposure of murine whole bodies to low dose radiation (0.2 gray) caused a time-related elevation (at zero and 3 days) followed by a reduction at 7 days in cell proliferation and IL-12 release. Although there was a pan decrease in IL-10, it was retained at higher levels at day 7 than zero time. These results indicate a state of immune stimulation following exposure to low dose radiation terminated by a remarkable tendency for immune suppression. When mice were exposed to as high as 5 gray radiation, there was a time-dependent and significant elevation in cell proliferation and IL-12 production till day 7 while IL-10 was reduced without remarkable tendency for recovery by day 7. These results indicate that a state of a typical immune stimulation developed after exposure to 5 gray of radiation.
When mice were exposed to as high as 10 gray radiation, there was a remarkable and time-related enhancement of cell proliferation while there was a significant elevation in IL-12 release at zero time that did not persist then after; IL-10 release was suppressed indicating again a-typical form of immune stimulation following exposure to 10 gray of radiation.
When mice were exposed to the highest dose of radiation (20 gray), there was a remarkable and time-dependent stimulation in cell proliferation associated with reduction in IL-12 release and an enhancement in IL-10 release indicating that mice exposed to higher doses of radiation suffered a standard state of immune suppression.
The results of the present study were further analyzed as a function of dose dependence at fixed time of recovery and showed that, immediately after exposure, the 20 gray dose gave the highest degree of cell proliferation although IL-12 was gradually increased by increasing the dose until dose 20 that showed remarkable decrease accompanied by significant elevation in IL-10 release capacity. These results indicate that high doses of 5 and 10 gray was still giving rise to increased IL-12 while the dose of 20 was typically suppressive. When the same comparison was made 3 days after irradiation, there was a clear cut and dose-dependent tendency for enhanced cell proliferation followed by a sharp decrease at the highest dose. This was associated with a remarkable stimulation of IL-12 production at low dose followed by a gradual suppression at higher doses. Also, IL-10 release was stimulated at low dose while gradually enhanced in a dose dependent manner with higher doses. At 7 day recovery time, there was a significant dose dependent enhancement in cell proliferation associated with a remarkably sharp elevation in IL-12 at the least of high doses followed by gradual suppression then after. On the other hand, no significant changes were recorded in IL-10 release capacity at comparable duration and doses.
At zero time recovery, all radiation doses were better than UVR in enhancing the cell proliferation and IL-12 release capacity while no priority for any of them was recorded as regards IL-10 production. At 3 days recovery, all doses of radiation were good enhancers for cell proliferation and IL-12 release except for the highest dose radiation dose that stimulated significantly lower cell proliferation than UVR without affecting IL-12 release. Concerning IL-10, The UVR and the low dose radiation were significantly better than higher radiation doses in stimulating IL-10. At the 7 day recovery time, only the low dose radiation gave lower cell proliferation than UVR while all high doses were better in the same context. Conversely, all radiation doses were less efficient than UVR in inducing IL-12 except for the 5 gray dose that was remarkably higher, while only the 10 gray dose of radiation was remarkably lower than UVR in stimulating IL-10 although no difference was recorded with other doses.