From mice and men to earth and space: joint NASA-NCI workshop on lung cancer risk resulting from space and terrestrial radiation.

On June 27-28, 2011, scientists from the National Cancer Institute (NCI), NASA, and academia met in Bethesda to discuss major lung cancer issues confronting each organization. For NASA, available data suggest that lung cancer is the largest potential cancer risk from space travel for both men and women and quantitative risk assessment information for mission planning is needed. In space, the radiation risk is from high energy and charge (HZE) nuclei (such as Fe) and high-energy protons from solar flares and not from gamma radiation.

Life sciences space missions. Overview.

It has been known for many years that weightlessness induces changes in numerous physiological systems: the cardiovascular system declines in both aerobic capacity and orthostatic tolerance; there is a reduction in fluid and electrolyte balance, hematocrit, and certain immune parameters; bone and muscle mass and strength are reduced; various neurological responses include space motion sickness and posture and gate alterations. These responses are caused by the hypokinesia of weightlessness, the cephalic fluid shift, the unloading of the vestibular system, stress, and the altered temporal environment.

Alterations in growth rate associated with a normally persisting circadian rhythm during spaceflight.

Background: Biological clocks time many physiological parameters with periodicities close to 24 h; those which persist in the absence of environmental cues are circadian. An earlier shuttle experiment (STS-9) examined circadian pacemaker function and growth rate of Neurospora crassa and demonstrated damped rhythm amplitudes, increased variability in period lengths and altered growth rates.

Hypothesis: Postflight studies suggested that accelerative forces of launch could have induced rhythm alterations.

Effects of spaceflight on the musculoskeletal system: NIH and NASA future directions.

Prolonged bed rest, undertaken by volunteers or resulting from injury and disease, can impair bone and muscle function and structure; extended travel in space also induces these effects. Fluid shifts and disrupted fluid balance may also contribute to observed musculoskeletal aberrations in the weightless environment. Some molecular and cellular events involved in the loading and unloading of the musculoskeletal system are under neural and endocrine influence or control, whereas other events are influenced by local growth factors.

Thermoregulatory responses of rhesus monkeys during spaceflight.

This study examines the activity, axillary temperature (T(ax)), and ankle skin temperature (Tsk) of two male Rhesus monkeys exposed to microgravity in space. The animals were flown on a Soviet biosatellite mission (COSMOS 1514). Measurements on the flight animals, as well as synchronous flight controls, were performed in the Soviet Union.

Neurosciences research in space: future directions.

Future research in the neurosciences can best be understood in the context of NASA's life sciences goals in the near term (1990-95), mid term (1995-2000), and long term (2000 and beyond). Since NASA is planning short-duration Spacelab and International Microgravity Laboratory (IML) flights for many years to come, the acute effects of exposure to microgravity will continue to be of experimental and operational interest in the near term. To this end, major new areas of research will be devoted to ground-based studies of preflight adaptation trainers and their efficacy in preventing or reducing the incidence of space motion sickness.

Nocturnal illumination does not necessarily stimulate the photoperiodic response, despite mimicking the effects of constant light on the circadian system in the male Syrian hamster.

In an effort to determine the inductive component(s) of photic input in long day seasonal breeders, adult male Syrian hamsters (Mesocricetus auratus) were exposed to one of nine lighting conditions for a duration of 10 weeks: a light-dark cycle of 14 hours of light followed by 10 hours of dark (LD 14:10, a long photoperiod); LD 10:14 (a short photoperiod); a high frequency light-dark cycle of 1 hour of light and 1 hour of dark (LD 1:1); a higher frequency light-dark cycle of 1 minute of light and 1 minute of dark (LD 1m:1m); constant light (LL); constant dark (DD); feedback lighting (LDFB; a condition that illuminates the cage in response to locomotor activity); a feedback lighting neighbor control (LDFB NC; the animal receives the same light pattern as a paired animal in LDFB, but has no control over it); or reverse feedback lighting (rLDFB; a condition that darkens an illuminated cage in response to locomotor activity). Exposure to LL, LD 1:1, LD 1m:1m, LDFB and rLDFB significantly and similarly lengthened the free-running period of the locomotor rhythm when compared to the period of animals in DD. The paired tests and accessory reproductive glands weights, spermiogenesis, seminiferous tubule diameter and serum concentrations of testosterone, prolactin, LH and FSH, suggest that LD 14:10, LL, LD 1:1, rLDFB and LDFB NC maintain reproductive function in the Syrian hamster, while LD 10:14, DD, LD 1m:1m and LDFB do not.

Gravitational biology and the mammalian circadian timing system.

Mammals have evolved under the influence of many selective pressures. Two of these pressures have been the static force of gravity and the daily variations in the environment due to the rotation of the earth. It is now clear that each of these pressures has led to specific adaptations which influence how organisms respond to changes in either gravity or daily time cues.

The biological clock of Neurospora in a microgravity environment.

The circadian rhythm of conidiation in Neurospora crassa is thought to be an endogenously derived circadian oscillation; however, several investigators have suggested that circadian rhythms may, instead, be driven by some geophysical time cue(s). An experiment was conducted on space shuttle flight STS-9 in order to test this hypothesis; during the first 7-8 cycles in space, there were several minor alterations observed in the conidiation rhythm, including an increase in the period of the oscillation, an increase in the variability of the growth rate and a diminished rhythm amplitude, which eventually damped out in 25% of the flight tubes. On day seven of flight, the tubes were exposed to light while their growth fronts were marked.

The effects of feedback lighting on the circadian drinking rhythm in the diurnal new world primate Saimiri sciureus.

Feedback lighting provides illumination primarily during the subjective night (i.e., the photosensitive portion of the circadian cycle) in response to a given behavior.

Assessment of the efficacy of medical countermeasures in space flight.

Changes in body fluids, electrolytes, and muscle mass are manifestations of adaptation to space flight and readaptation to the 1-g environment. The purposes of this paper are to review the current knowledge of biomedical responses to short- and long-duration space missions and to assess the efficacy of countermeasures to 1-g conditioning. Exercise protocols, fluid hydration, dietary and potential pharmacologic measures are evaluated, and directions for future research activities are recommended.

Light effects on circadian timing system of a diurnal primate, the squirrel monkey.

We examined light effects on the circadian timing system of the squirrel monkey. A phase-response curve to 1-h pulses of light was constructed for the drinking rhythm of six animals. The phase-response curve was the same type as that exhibited by nocturnal rodents, with phase delays occurring early in the subjective night and phase advances late in the subjective night.

Role of heat loss and heat production in generation of the circadian temperature rhythm of the squirrel monkey.

To study heat production and heat loss in determination of the daily body temperature rhythm, we examined colonic temperature, skin (tail, foot and abdomen) temperatures and oxygen consumption in chair-restrained squirrel monkeys maintained in isolation in an environmental chamber with a 24-hr light-dark cycle (LD 12:12), maintained at a constant thermoneutral temperature (26 degrees C). In all experiments repeated high amplitude (2 degrees C) diurnal rhythms in colonic temperature were observed. Heat loss, estimated from changes in skin temperature, also displayed a circadian rhythm, although there was considerable variation in waveform.

Circadian rhythms of drinking and body temperature of the owl monkey (Aotus trivirgatus).

The rhythms of drinking and body temperature of 4 male owl monkeys (Aotus trivirgatus) were examined under conditions of LD 12:12 (L = 100 lx, D = 0.1 lx), DD (0.1 lx) and LL (100 lx).

Circadian rhythms in body temperature of the pigtailed macaque (Macaca nemestrina) exposed to different ambient temperatures.

The body and leg skin temperatures of five pigtailed macaques (Macaca nemestrina) were measured at various ambient air temperatures ranging from 22 to 32°C over 24-h periods. The rhythm in core body temperature persisted in all ambient air temperatures, and the rhythm in leg skin temperature was suppressed at the higher and lower ambient temperatures. This suggests that at the upper and lower regions of the thermoneutral zone, either a rhythm in heat production or a heat loss rhythm other than leg skin temperature is regulating the core body temperature rhythm.

Neurospora circadian rhythms in space: a reexamination of the endogenous-exogenous question.

To test the functioning of circadian rhythms removed from periodicities of the earth's 24-hour rotation, the conidiation rhythm of the fungus Neurospora crassa was monitored in constant darkness during spaceflight. The free-running period of the rhythm was the same in space as on the earth, but there was a marked reduction in the clarity of the rhythm, and apparent arrhythmicity in some tubes. At the current stage of analysis of our results there is insufficient evidence to determine whether the effect seen in space was related to removal from 24-hour periodicities and whether the circadian timekeeping mechanism, or merely its expression, was affected.

Preliminary characterization of persisting circadian rhythms during space flight.

In order to evaluate the function of the circadian timing system in space, the circadian rhythm of conidiation of the fungus Neurospora crassa was monitored in constant darkness on the STS 9 flight of the Space Shuttle Columbia. During the first 7 days of spaceflight many tubes showed a marked reduction in the apparent amplitude of the conidiation rhythm, and some cultures appeared arrhythmic. There was more variability in the growth rate and circadian rhythms of individual cultures in space than is usually seen on earth.

Auditory entrainment of primate drinking rhythms following partial suprachiasmatic nuclei lesions.

In the absence of other environmental cycles, daily variations in auditory stimuli are normally not capable of entraining the circadian rhythms of drinking behavior in the squirrel monkey (Saimiri sciureus). However, the drinking rhythm appears to become entrainable by previously ineffective auditory cues after lesions are placed which destroy only the caudal portion of the hypothalamic suprachiasmatic nuclei. The results suggest specificity of function within the SCN and an increased influence of auditory stimuli in animals with impaired SCN function.

Circadian entrainment of the squirrel monkey by extreme photoperiods: interactions between the phasic and tonic effects of light.

To examine the role that the phasic and tonic aspects of the light-dark (LD) cycle play in entraining the circadian timing system of primates, squirrel monkeys (Saimiri sciureus) were exposed to 24 hr LD cycles in which the light duration (photoperiod) was varied from 1 sec to 23 hr. The monkeys were maintained in isolation and the circadian rhythm of drinking was monitored. The photoperiod was first gradually shortened until constant darkness was reached.

Cellular autonomy of the Gonyaulax circadian clock.

Because of the long term persistence of free-running circadian rhythms in populations of unicells, several investigators have considered, but not demonstrated, a possible role for intercellular interaction in maintaining synchrony between individual cells. The experiments described here were designed to test more critically the possibility that there is interaction between cells, including those possessing only small phase differences. None was detected; the bioluminescent glow of the mixed cultures matched the algebraic sum of the independent control cultures.