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At least 163 records · Page 9

Functional Assessment of NK and LAK Cells Following Space Flight

Space flight associated stress alters some aspects of the human immune response. In this study, we determined the effects of 10 days aboard the Space Shuttle on the cytotoxic activity of NK and LAK cells. PBMCs were collected from 10-ml blood specimens from 5 astronauts 10 days before launch, immediately after landing, and again at 3 days after landing and stored at -80 C. All PBMCs were thawed simultaneously, and the cytotoxic activities of NK and LAK cells were measured by a 4 hour Cr-51 release assay. K562 cells were used to assess NK cell cytotoxicity. Following 4 days of IL-2 activation, the LAK cell cytotoxic activity was determined using K562 cells and Daudi cells as the target cells. NK cell cytotoxicity decreased at landing (p<.05) in 3/5 astronauts, and recovered to preflight levels by 3 days following landing; NK cell cytotoxicity was increased (p=0.1) in the remaining 2 astronauts at landing. In 4/5 astronauts, LAK cytotoxic activity was decreased at landing against K562 cells (p = 0.13) and Daudi cells (p = 0.08). Phenotyping of PBMC's and LAK cells showed alterations in some surface markers and adhesion molecules (CD11b, CD11c, CD11a, CD16, L-selectin, and CD3).

Kaur, Indreshpal↗

Precise Orbit Determination for GEOSAT Follow-On Using Satellite Laser Ranging Data and Intermission Altimeter Crossovers

The US Navy's GEOSAT Follow-On Spacecraft was launched on February 10, 1998 with the primary objective of the mission to map the oceans using a radar altimeter. Following an extensive set of calibration campaigns in 1999 and 2000, the US Navy formally accepted delivery of the satellite on November 29, 2000. Satellite laser ranging (SLR) and Doppler (Tranet-style) beacons track the spacecraft. Although limited amounts of GPS data were obtained, the primary mode of tracking remains satellite laser ranging. The GFO altimeter measurements are highly precise, with orbit error the largest component in the error budget. We have tuned the non-conservative force model for GFO and the gravity model using SLR, Doppler and altimeter crossover data sampled over one year. Gravity covariance projections to 70x70 show the radial orbit error on GEOSAT was reduced from 2.6 cm in EGM96 to 1.3 cm with the addition of SLR, GFO/GFO and TOPEX/GFO crossover data. Evaluation of the gravity fields using SLR and crossover data support the covariance projections and also show a dramatic reduction in geographically-correlated error for the tuned fields. In this paper, we report on progress in orbit determination for GFO using GFO/GFO and TOPEX/GFO altimeter crossovers. We will discuss improvements in satellite force modeling and orbit determination strategy, which allows reduction in GFO radial orbit error from 10-15 cm to better than 5 cm.

Lemoine, Frank G.↗

Development of a Model Following Control Law for Inflight Simulation and Flight Controls Research

The U.S. Army and NASA are currently developing the Rotorcraft Aircrew Systems Concepts Airborne Laboratory (RASCAL) at the Ames Research Center. RASCAL, shown in Figure 1, is a UH-60, which is being modified in a phased development program to have a research fly-by-wire flight control system, and an advanced navigation research platform. An important part of the flight controls and handling qualities research on RASCAL will be an FCS design for the aircraft to achieve high bandwidth control responses and disturbance rejection characteristics. Initially, body states will be used as feedbacks, but research into the use of rotor states will also be considered in later stages to maximize agility and maneuverability. In addition to supporting flight controls research, this FCS design will serve as the inflight simulation control law to support basic handling qualities, guidance, and displays research. Research in high bandwidth controls laws is motivated by the desire to improve the handling qualities in aggressive maneuvering and in severely degraded weather conditions. Naturally, these advantages will also improve the quality of the model following, thereby improving the inflight simulation capabilities of the research vehicle. High bandwidth in the control laws provides tighter tracking allowing for higher response bandwidths which can meet handling qualities requirements for aggressive maneuvering. System sensitivity is also reduced preventing variations in the response from the vehicle due to changing flight conditions. In addition, improved gust rejection will result from this reduced sensitivity. The gust rejection coupled with a highly stable system will make more precise maneuvering and pointing possible in severely degraded weather conditions. The difficulty in achieving higher bandwidths from the control laws in the feedback and in the responses arises from the complexity of the models that are needed to produce a satisfactory design. In this case, high quality models that include rotor dynamics in a physically meaningful context must be available. A non-physical accounting of the rotor, such as lumping the effect as a time delay, is not likely to produce the desired results. High order simulation models based on first principals are satisfactory for the initial design phase in order to work out the control law design concept and get an initial set of gains. These models, however, have known deficiencies, which must be resolved in the final control law design. The error in the pitch-roll cross coupling is one notable deficiency that even sophisticated rotorcraft models including complex wake aerodynamics have yet to capture successfully. This error must be accounted for to achieve the desired decoupling. The approach to design the proposed inflight simulation control law is based on using a combination of simulation and identified models. The linear and nonlinear higher order models were used to develop an explicit model following control structure. This structure was developed to accommodate the design of control laws compliant to many of the quantitative requirements in ADS-33C. Furthermore, it also allows for control law research using rotor-state feedback and other design methodologies such as Quantitative Feedback and H-Infinity. Final gain selection will be based on higher order identified models which include rotor degrees of freedom.

Takahashi, Mark↗

From Global Reconnaissance to Sample Return: A Proposal for a Post-2009 Strategy to Follow the Water on Mars

Since the mid-1990's, the stated strategy of the Mars Exploration Program has been to Follow the Water. Although this strategy has been widely publicized, its degree of influence -- and the logic behind its current implementation (as reflected in mission planning, platform and instrument selection, and allocation of spacecraft resources) remains unclear. In response to this concern, we propose an integrated strategy for the post-2009 exploration of Mars that identifies the scientific objectives, rationale, sequence of missions, and specific investigations, that we believe provides the maximum possible science return by pursuing the most direct, cost-effective, and technically capable approach to following the water. This strategy is based on the orbital identification, high-resolution surface investigation, and ultimate sampling of the highest priority targets: near-surface liquid water and massive ground ice (potentially associated with the discharge of the outlflow channels or the relic of a former ocean). The analysis of such samples, in conjunction with the data acquired by the necessary precursor investigations (to identify the locations and characterize the environments of the optimum sampling sites), is expected to address a majority of the goals and high priority science objectives identified by MEPAG.

S M Clifford↗

Astrometric Follow-Up of Faint Near Earth Objects

The observing program at Mt. Hopkins using the 48" reflector and funded by the Near- Earth Object Observation Program continues to excel. As in the past, all requested observing time was granted. Minor improvements continue to be made. For example, the telescope is set up to track and non-sidereal rates. This allows the user to track on the target object, rather than relying exclusively on the shift- and-stack technique. Other improvements made by the staff include automatic focus routines, automatic seeing-measurement routines, and improvement in dome seeing and mirror stabilization. The net result is better focus, better seeing, and the ability to expose longer in order to acquire the faintest and most important objects. During the proposal period, this program ranked again very high worldwide in terms of faint Near Earth Objects observed. During this latest proposal cycle, fewer objects were observed than previous cycles, but this was due to the strict targeting of only the faintest observable objects. The follow-up programs of observatory codes 926 (led by P. Holvorcem) and 291 (led by Dr. B. McMillan) have greatly increased their capacity, and as a result less bright objects are in urgent need of follow-up than in years past. Even with this new object selection and additional competition, code 696 still ranked second to code 291 in terms of objects observed fainter than V = 20. Minimal scripting is now in place to allow the telescope to run autonomously for 30-45 minutes at a time.

Morgan, T.↗

Sympathetic responses to Valsalva's manoeuvre following bed rest

The purpose of this study was to examine whether 14 days of head-down tilt bed rest (HDBR) alters autonomic regulation during Valsalva's manoeuvre (VM) and if this would predict blood pressure control during a 60 degrees head-up tilt (HUT) test. To examine autonomic control of blood pressure, we measured the changes in systolic (delta SBP) and diastolic (delta DBP) blood pressure between baseline and the early straining (Phase IIE) period of VM (20 sec straining to 40 mmHg; N = 7) in conjunction with changes in muscle sympathetic nerve activity (MSNA; microneurography) burst frequency (B/min) and total activity (% delta) from baseline over the 20-sec straining period. MSNA data were successfully recorded from 6 of the 7 individuals. The averaged responses from three repeated VMs performed in the supine position were compared between the pre- and post-HDBR tests. Compared with the pre-HDBR test, a greater reduction in SBP, DBP, and MAP was observed during Phase IIE following HDBR, p < 0.05. The increase in MSNA burst frequency during straining was augmented in the post- compared with the pre-HDBR test, p < 0.0001, as was the Phase IV blood pressure overshoot, p < 0.05. Although all subjects completed the 20-min pre-HDBR tilt test without evidence of hypotension or orthostatic intolerance, the post-HDBR test was stopped early in 5 of the 7 subjects due to systolic hypotension. The responses during the VM suggest that acute autonomic adjustments to rapid blood pressure changes are preserved after bed rest. Furthermore, MSNA and blood pressure responses during VM did not predict blood pressure control during orthostasis following HDBR.

NASA Discipline Musculoskeletal↗

Fidelity and enhanced sensitivity of differential transcription profiles following linear amplification of nanogram amounts of endothelial mRNA

Although mRNA amplification is necessary for microarray analyses from limited amounts of cells and tissues, the accuracy of transcription profiles following amplification has not been well characterized. We tested the fidelity of differential gene expression following linear amplification by T7-mediated transcription in a well-established in vitro model of cytokine [tumor necrosis factor alpha (TNFalpha)]-stimulated human endothelial cells using filter arrays of 13,824 human cDNAs. Transcriptional profiles generated from amplified antisense RNA (aRNA) (from 100 ng total RNA, approximately 1 ng mRNA) were compared with profiles generated from unamplified RNA originating from the same homogeneous pool. Amplification accurately identified TNFalpha-induced differential expression in 94% of the genes detected using unamplified samples. Furthermore, an additional 1,150 genes were identified as putatively differentially expressed using amplified RNA which remained undetected using unamplified RNA. Of genes sampled from this set, 67% were validated by quantitative real-time PCR as truly differentially expressed. Thus, in addition to demonstrating fidelity in gene expression relative to unamplified samples, linear amplification results in improved sensitivity of detection and enhances the discovery potential of high-throughput screening by microarrays.

Evaluation Studies↗

Computational Model of the Modulation of Gene Expression Following DNA Damage

High linear energy transfer (LET) radiation, such as heavy ions or neutrons, has an increased biological effectiveness compared to X rays for gene mutation, genomic instability, and carcinogenesis. In the traditional paradigm, mutations or chromosomal aberrations are causative of late effects. However, in recent years experimental evidence has demonstrated the important role of the description of the modification of gene expression by radiation in understanding the mechanisms of radiation action. In this report, approaches are discussed to the mathematical description of mRNA and protein expression kinetics following DNA damage. Several hypotheses for models of radiation modulation of protein expression are discussed including possible non-linear processes that evolve from the linear dose responses that follow the initial DNA damage produced by radiation.

NASA Center JSC↗

Neural readaptation to Earth's gravity following return from space

The consequence of exposure to microgravity on the otolith organs was studied by recording the responses of vestibular nerve afferents supplying the utricular otolith organ to inertial accelerations in four toadfish, Opsanus tau, sequentially for 5 days following two National Aeronautics and Space Administration shuttle orbital flights. Within the first day postflight, the magnitude of response to an applied translation was on average three times greater than for controls. The reduced gravitational acceleration in orbit apparently resulted in an upregulation of the sensitivity of utricular afferents. By 30 h postflight, responses were statistically similar to control. The time course of return to normal afferent sensitivity parallels the reported decrease in vestibular disorientation in astronauts following return from space.

manned↗

Altered central nervous system processing of baroreceptor input following hindlimb unloading in rats

The effect of cardiovascular deconditioning on central nervous system processing of baroreceptor afferent activity was evaluated following 14 days of hindlimb unloading (HU). Inactin-anesthetized rats were instrumented with catheters, renal sympathetic nerve electrodes, and aortic depressor nerve electrodes for measurement of mean arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and aortic depressor nerve activity (ADNA). Baroreceptor and baroreflex functions were assessed during infusion of phenylephrine and sodium nitroprusside. Central processing of baroreceptor afferent input was evaluated by linear regression relating RSNA to ADNA. The maximum baroreflex-elicited increase in RSNA was significantly reduced in HU rats (122 +/- 3.8 vs. 144 +/- 4.9% of baseline RSNA), whereas ADNA was not altered. The slope (-0.18 +/- 0.04 vs. -0.40 +/- 0.04) and y-intercept (121 +/- 3.2 vs. 146 +/- 4.3) of the linear regression relating increases in efferent RSNA to decreases in afferent ADNA during hypotension were significantly reduced in HU rats. There were no differences during increases in arterial pressure. Results demonstrate that the attenuation in baroreflex-mediated increases in RSNA following HU is due to changes in central processing of baroreceptor afferent information rather than aortic baroreceptor function.

NASA Discipline Cardiopulmonary↗

Changes in peak oxygen uptake and plasma volume in fit and unfit subjects following exposure to a simulation of microgravity

To test the hypothesis that the magnitude of reduction in plasma volume and work capacity following exposure to simulated microgravity is dependent on the initial level of aerobic fitness, peak oxygen uptake (VO2peak) was measured in a group of physically fit subjects and compared with VO2peak in a group of relatively unfit subjects before and after 10 days of continuous 6 degrees head-down tilt (HDT). Ten fit subjects (40 +/- 2 year) with mean +/- SE VO2peak = 48.9 +/- 1.7 mL kg-1 min-1 were matched for age, height, and lean body weight with 10 unfit subjects (VO2peak = 37.7 +/- 1.6 mL kg-1 min-1). Before and after HDT, plasma, blood, and red cell volumes and body composition were measured and all subjects underwent a graded supine cycle ergometer test to determine VO2peak period needed. Reduced VO2peak in fit subjects (-16.2%) was greater than that of unfit subjects (-6.1%). Similarly, reductions in plasma (-18.3%) and blood volumes (-16.0%) in fit subjects were larger than those of unfit subjects (blood volume = -5.6%; plasma volume = -6.6%). Reduced plasma volume was associated with greater negative body fluid balance during the initial 24 h of HDT in the fit group (912 +/- 154 mL) compared with unfit subjects (453 +/- 200 mL). The percentage change for VO2peak correlated with percentage change in plasma volume (r = +0.79). Following exposure to simulated microgravity, fit subjects demonstrated larger reductions in VO2peak than unfit subjects which was associated with larger reductions in plasma and blood volume. These data suggest that the magnitude of physical deconditioning induced by exposure to microgravity without intervention of countermeasures was influenced by the initial fitness of the subjects.

Non-NASA Center↗

Cardiovascular function following reduced aerobic activity

PURPOSE: The aim of this study was to test the hypothesis that a sustained reduction of physical activity (deconditioning) would alter the cardiovascular regulatory function. METHODS: Nineteen young, healthy volunteers participated in physical deconditioning for a period of 8 wk. Before (pre) and following (post) physical deconditioning, the responses of heart rate (HR), mean arterial pressure (MAP, measured by Finapres), central venous pressure (CVP), stroke volume (SV, Doppler), and forearm blood flow (FBF, plethysmography) were determined during lower body negative pressure (LBNP). The carotid baroreflex (CBR) function was assessed using a train of pulsatile neck pressure (NP) and suction, and the aortic baroreflex control of HR was assessed during steady-state phenylephrine (PE) infusion superimposed by LBNP and NP to counteract the PE increased CVP and carotid sinus pressure, respectively. RESULTS: Active physical deconditioning significantly decreased maximal oxygen uptake (-7%) and LBNP tolerance (-13%) without a change in baseline hemodynamics. Plasma volume (-3% at P = 0.135), determined by Evans Blue dilution, and blood volume (-4% at P = 0.107) were not significantly altered. During LBNP -20 to -50 torr, there was a significantly greater drop of SV per unit decrease in CVP in the post- (14.7 +/- 1.6%/mm Hg) than predeconditioning (11.2 +/- 0.7%/mm Hg) test accompanied by a greater tachycardia. Deconditioning increased the aortic baroreflex sensitivity (pre vs post: -0.61 +/- 0.12 vs -0.84 +/- 0.14 bpm.mm-1 Hg, P = 0.009) and the slope of forearm vascular resistance (calculated from [MAP-CVP]/FBF) to CVP (-2.75 +/- 0.26 vs -4.94 +/- 0.97 PRU/mm Hg, P = 0.086). However, neither the CBR-HR (-0.28 +/- 0.03 VS -0.39 +/- 0.10 bpm.mm-1 Hg) nor the CBR-MAP (-0.37 +/- 0.16 vs -0.25 +/- 0.07 mm Hg/mm Hg) gains were statistically different between pre- and postdeconditioning. CONCLUSIONS: We concluded that the functional modification of the cardiac pressure-volume relationship resulted in the reduced LBNP tolerance, despite the accentuated aortic and cardiopulmonary baroreflex function following deconditioning.

Non-NASA Center↗

Locomotor head-trunk coordination strategies following space flight

During locomotion, angular head movements act in a compensatory fashion to oppose the vertical trunk translation that occurs during each step in the gait cycle. This coordinated strategy between head and trunk motion serves to aid gaze stabilization and perhaps simplifies the sensory coordinate transformation between the head and trunk, allowing efficient descending motor control during locomotion. Following space flight, astronauts often experience oscillopsia during locomotion in addition to postural and gait instabilities, suggesting a possible breakdown in head-trunk coordination. The goal of the present investigation was to determine if exposure to the microgravity environment of space flight induces alteration in head-trunk coordination during locomotion. Astronaut subjects were asked to walk (6.4 km/h, 20 s trials) on a motorized treadmill while visually fixating on a centrally located earthfixed target positioned either 2 m (FAR) or 30 cm (NEAR) from the eyes. In addition, some trials were also performed during periodic visual occlusion. Head and trunk kinematics during locomotion were determined with the aid of a video-based motion analyzing system. We report data collected preflight (10 days prior to launch) and postflight (2 to 4 hours after landing). The coherence between pitch head and vertical trunk movements during gaze fixation of both FAR and NEAR targets was significantly reduced following space flight indicating decreased coordination between the head and trunk during postflight locomotion. Astronauts flying on their first mission showed greater alterations in the frequency spectra of pitch head movements as compared to their more experienced counterparts. These modifications in the efficacy of head movement control may account for the reported disruption in gaze performance during locomotion and may contribute to postflight postural and gait dysfunction.

NASA Discipline Neuroscience↗

Recovery of postural equilibrium control following space flight

DSO 605 represents the first large study of balance control following spaceflight. Data collected during DSO 605 confirm the theory that postural ataxia following short duration spaceflight is of vestibular origin. We used the computerized dynamic posturography technique developed by Nashner et al. to study the role of the vestibular system in balance control in astronauts during quiet stance before and after spaceflight. Our results demonstrate unequivocally that balance control is disrupted in all astronauts immediately after return from space. The most severely affected returning crew members performed in the same way as vestibular deficient patients exposed to this test battery. We conclude that otolith mediated spatial reference provided by the terrestrial gravitational force vector is not used by the astronauts balance control systems immediately after spaceflight. Because the postflight ataxia appears to be mediated primarily by CNS adaptation to the altered vestibular inputs caused by loss of gravitational stimulation, we believe that intermittent periods of exposure to artificial gravity may provide an effective in-flight countermeasure. Specifically, we propose that in-flight centrifugation will allow crew members to retain their terrestrial sensory-motor adapted states while simultaneously developing microgravity adapted states. The dual-adapted astronaut should be able to make the transition from microgravity to unit gravity with minimal sensory-motor effects. We have begun a ground based program aimed at developing short arm centrifuge prescriptions designed to optimize adaptation to altered gravitational environments. Results from these experiments are expected to lead directly to in-flight evaluation of the proposed centrifuge countermeasure. Because our computerized dynamic posturography system was able to (1) quantify the postflight postural ataxia reported by crew members and observed by flight surgeons and scientists, (2) track the recovery of normal (preflight) balance control, (3) differentiate between rookie and veteran subjects, and (4) provide normative and clinical databases for comparison, and because our study successfully characterized postflight balance control recovery in a large cross-section of Shuttle crew members, we recommend that this system and protocol be adopted as a standard dependent measure for evaluating the efficacy of countermeasures and/or evaluating the postflight effects of changing mission durations or activities.

Paloski, William H.↗

M.I.T./Canadian vestibular experiments on the Spacelab-1 mission: 6. Vestibular reactions to lateral acceleration following ten days of weightlessness

Tests of otolith function were performed pre-flight and post-flight on the science crew of the first Spacelab Mission with a rail-mounted linear acceleration sled. Four tests were performed using horizontal lateral (y-axis) acceleration: perception of linear motion, a closed loop nulling task, dynamic ocular torsion, and lateral eye deviations. The motion perception test measured the time to detect the onset and direction of near threshold accelerations. Post-flight measures of threshold and velocity constant obtained during the days immediately following the mission showed no consistent pattern of change among the four crewmen compared to their pre-flight baseline other than an increased variability of response. In the closed loop nulling task, crewmen controlled the motion of the sled and attempted to null a computer-generated random disturbance motion. When performed in the light, no difference in ability was noted between pre-flight and post-flight. In the dark, however, two of the four crewmen exhibited somewhat enhanced performance post-flight. Dynamic ocular torsion was measured in response to sinusoidal lateral acceleration which produces a gravitionertial stimulus equivalent to lateral head tilt without rotational movement of the head. Results available for two crewmen suggest a decreased amplitude of sinusoidal ocular torsion when measured on the day of landing (R+0) and an increasing amplitude when measured during the week following the mission.

short duration↗

Adaptive Changes in Sensorimotor Coordination and Motion Sickness Following Repeated Exposures to Virtual Environments

Virtual environments offer unique training opportunities, particularly for training astronauts and preadapting them to the novel sensory conditions of microgravity. Two unresolved human factors issues in virtual reality (VR) systems are: 1) potential "cybersickness", and 2) maladaptive sensorimotor performance following exposure to VR systems. Interestingly, these aftereffects are often quite similar to adaptive sensorimotor responses observed in astronauts during and/or following space flight. Initial interpretation of novel sensory information may be inappropriate and result in perceptual errors. Active exploratory behavior in a new environment, with resulting feedback and the formation of new associations between sensory inputs and response outputs, promotes appropriate perception and motor control in the new environment. Thus, people adapt to consistent, sustained alterations of sensory input such as those produced by microgravity, unilateral labyrinthectomy and experimentally produced stimulus rearrangements. The purpose of this research was to compare disturbances in sensorimotor coordination produced by dome and head-mounted virtual environment displays and to examine the effects of exposure duration, and repeated exposures to VR systems. The first study examined disturbances in balance control, and the second study examined disturbances in eye-head-hand (EHH) and eye-head coordination.

Harm, D. L.↗

Constraints on an Optical Afterglow and on Supernova Light Following the Short Burst GRB 050813

We report early follow-up observations of the error box of the short burst 050813 using the telescopes at Calar Alto and at Observatorio Sierra Nevada (OSN), followed by deep VLT/FORS2 I-band observations obtained under very good seeing conditions 5.7 and 11.7 days after the event. No evidence for a GRB afterglow was found in our Calar Alto and OSN data, no rising supernova component was detected in our FORS2 images. A potential host galaxy can be identified in our FORS2 images, even though we cannot state with certainty its association with GRB 050813. IN any case, the optical afterglow of GRB 050813 was very faint, well in agreement with what is known so far about the optical properties of afterglows of short bursts. We conclude that all optical data are not in conflict with the interpretation that GRB 050813 was a short burst.

Ferrero, P.↗

Involvement of DNA-PK(sub cs) in DSB Repair Following Fe-56 Ion Irradiation

When cells are exposed to radiation, cellular lesions are induced in the DNA including double strand breaks (DSBs), single strand breaks and clustered DNA damage, which if not repaired with high fidelity may lead to detrimental biological consequences. Complex DSBs are induced by ionizing radiation and characterized by the presence of base lesions close to the break termini. They are believed to be one of the major causes of the biological effects of IR. The complexity of DSBs increases with the ionization density of the radiation and these complex DSBs are distinct from the damage induced by sparsely ionizing gamma-radiation. It has been hypothesized that complex DSBs produced by heavy ions in space pose problems to the DNA repair machinery. We have used imm uno-cyto-chemical staining of phosphorylated histone H2AX (gamma-H2AX) foci, as a marker of DSBs. We have investigated the formation and loss of gamma-H2AX foci and RAD51 foci (a protein involved in the homologous recombination pathway) in mammalian cells induced by low fluences of low-LET gamma-radiation and high-LET Fe-56 ions (1GeV/n, 151 keV/micron LET). M059J and M059K cells, which are deficient and proficient in DNA-PK(sub cs) activity respectively, were used to examine the role of DNA-PK(sub cs), a key protein in the non-homologous end joining (NHEJ) pathway of DSB repair, along with HF19 human fibroblasts. Followi ng irradiation with Fe-56 ions the rate of repair was slower in M059J cells compared with that in M059K, indicating a role for DNA-PK(sub cs) in the repair of DSB induced by Fe-56 ions. However a small percentage of DSBs induced are rejoined within 5 h although many DSBs still persist up to 24 h. When RAD51 was examined in M059J/K cells, RAD51 foci are visible 24 hours after irradiation in approximately 40% of M059J cells compared with <5% of M059K cells indicating that persistent DSBs or those formed at stalled replication forks recruit RAD51 in DNA-PK(sub cs) deficient cells. Following 1 Gy gamma-radiation the induction of gamma-H2AX foci is similar in M059J and M059K cells. However, the repair rate of DSBs is slower in M059J cells than in M059K as shown previously but faster than seen with DSB induced by 56Fe ions. Vanillin, an inhibitor of DNA-PK(sub cs), reduces significantly the rate of DSB repair in HF19 cells following 1 Gy gamma-radiation but at 0.25 Gy gamma-irradiation the rate of DSB repair is similar in the presence or absence vanillin, thus suggesting the repair of a sub-set of DSBs induced by low dose, low-LET radiation does not require DNA-PK(sub cs). This sub-set of DSBs is formed in lower yield with high LET radiation. T he complexity of DNA DSBs induced by HZE radiation will be discussed in terms of reduced repair efficiency and provide scope to model different sub-classes of DSBs as precursors that may lead to the detrimental health effects of HZE radiation.

O'Neill, Peter↗