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PubMed1990

Reproduction in the space environment: Part II. Concerns for human reproduction.

Long-duration space flight and eventual colonization of our solar system will require successful control of reproductive function and a thorough understanding of factors unique to space flight and their impact on gynecologic and obstetric parameters. Part II of this paper examines the specific environmental factors associated with space flight and the implications for human reproduction. Space environmental hazards discussed include radiation, alteration in atmospheric pressure and breathing gas partial pressures, prolonged toxicological exposure, and microgravity. The effects of countermeasures necessary to reduce cardiovascular deconditioning, calcium loss, muscle wasting, and neurovestibular problems are also considered. In addition, the impact of microgravity on male fertility and gamete quality is explored. Due to current constraints, human pregnancy is now contraindicated for space flight. However, a program to explore effective countermeasures to current constraints and develop the required health care delivery capability for extended-duration space flight is suggested. A program of Earth- and space-based research to provide further answers to reproductive questions is suggested.

Extraterrestrial Environment↗

PubMed2001

Extracellular signaling through the microenvironment: a hypothesis relating carcinogenesis, bystander effects, and genomic instability.

Cell growth, differentiation and death are directed in large part by extracellular signaling through the interactions of cells with other cells and with the extracellular matrix; these interactions are in turn modulated by cytokines and growth factors, i.e. the microenvironment. Here we discuss the idea that extracellular signaling integrates multicellular damage responses that are important deterrents to the development of cancer through mechanisms that eliminate abnormal cells and inhibit neoplastic behavior. As an example, we discuss the action of transforming growth factor beta (TGFB1) as an extracellular sensor of damage. We propose that radiation-induced bystander effects and genomic instability are, respectively, positive and negative manifestations of this homeostatic process. Bystander effects exhibited predominantly after a low-dose or a nonhomogeneous radiation exposure are extracellular signaling pathways that modulate cellular repair and death programs. Persistent disruption of extracellular signaling after exposure to relatively high doses of ionizing radiation may lead to the accumulation of aberrant cells that are genomically unstable. Understanding radiation effects in terms of coordinated multicellular responses that affect decisions regarding the fate of a cell may necessitate re-evaluation of radiation dose and risk concepts and provide avenues for intervention.

Bystander Effect↗

PubMed2003

The impact of the new biology on radiation risks in space.

Radiation is considered to be one of three or four major hazards for personnel in space and has emerged as the most critical issue to be resolved for long-term missions, both orbital and interplanetary. Space habitats are stressful and dangerous environments. Health and medical consequences arising from microgravity, stress, and trauma include weakened immune systems, increased viral activity, and loss of bone mass. The greatest risks from radiation are generally assumed to be cancers and possibly damage to the central nervous system. Synergistic effects arising from the other environmental hazards along with abscopal and exogenic factors are likely. Space programs represent an exceptional opportunity for examining the biological consequences of low-dose exposures of humans to radiation at every level of progression. Although astronauts are a relatively small population, they are healthy, physically active volunteers who undergo extensive testing and medical examinations before, during, and after protracted exposures with periodic follow-up examinations. The radiation environments along with other hazards are likewise monitored and documented. Extensive international research programs are in progress. Seven years ago the U.S. National Aeronautics and Space Administration established the National Space Biomedical Research Institute through a cooperative agreement with a consortium of research and academic institutions in order to address radiation issues through a concerted, programmatic effort. Advanced technologies are rapidly being incorporated into these programs to determine the significance of new biological data and to evaluate the interplay among the different medical hazards. Programmatic in vivo and in vitro studies of the processes leading to carcinogenesis are in progress. Drugs and dietary supplements are being examined at the cellular and in vivo levels to assess their potential as dose-modifying agents. The infrastructure of this new approach, recent results, and research in progress are reviewed and discussed.

Academies and Institutes↗

PubMed2001

BNL accelerator-based radiobiology facilities.

For the past several years, the Alternating Gradient Synchrotron (AGS) at Brookhaven National Laboratory (USA) has provided ions of iron, silicon and gold, at energies from 600 MeV/nucleon to 10 GeV/nucleon, for the US National Aeronautics and Space Administration (NASA) radiobiology research program. NASA has recently funded the construction of a new dedicated ion facility, the Booster Applications Facility (BAF). The Booster synchrotron will supply ion beams ranging from protons to gold, in an energy range from 40-3000 MeV/nucleon with maximum beam intensities of 10(10) to 10(11) ions per pulse. The BAF Project will be described and the future AGS and BAF operation plans will be presented.

Animals↗

PubMed2005

SCHIP: statistics for chromosome interphase positioning based on interchange data.

MOTIVATION: The position of chromosomes in the interphase nucleus is believed to be associated with a number of biological processes. Here, we present a web-based application that helps analyze the relative position of chromosomes during interphase in human cells, based on observed radiogenic chromosome aberrations. The inputs of the program are a table of yields of pairwise chromosome interchanges and a proposed chromosome geometric cluster. Each can either be uploaded or selected from provided datasets. The main outputs are P-values for the proposed chromosome clusters. SCHIP is designed to be used by a number of scientific communities interested in nuclear architecture, including cancer and cell biologists, radiation biologists and mathematical/computational biologists.

Chromosome Aberrations↗

PubMed1999

Preparing for Mars: the physiologic and medical challenges.

As the twentieth century closes, retrospectives cite the Apollo moon missions as one of the important events of the past 100 years. A trip to Mars, however, would be even more challenging and significant. A round-trip Mars journey would require nearly three years away from Earth, a significant leap in complexity compared to the two week long Moon trips or the record-breaking fourteen-month flight on Mir. What would be the physiologic and medical challenges of a Mars flight? Two key areas of physiology present the greatest potential problems--calcium metabolism and radiation exposure. Data from Mir missions show that bone loss continues in space despite an aggressive countermeasure program. Average losses were 0.35% per month, but some load bearing areas lost >1% per month. A 1% loss rate, if it continued unabated for 30 months, could produce osteoporosis. Smaller losses could still increase fracture risk. Some bone loss can be well tolerated, particularly if the bone can be regained after the mission. But the effectiveness of post-flight rehabilitation to restore the density and quality of bone after spaceflight is not well known. Bone loss estimates are based on continuous weightlessness exposure, but this is not a requirement for a Mars trip. Most of the time on a Mars trip will be spent in the 1/3 Earth's gravity environment on Mars, and either intermittent or continuous artificial gravity can be provided for the transit between planets (although at an engineering cost). The dosing of the gravity exposure (e.g. the level and duration), however, has not been established. Radiation protection also requires a balance between engineering cost and human health. Excessive shielding could add billions of dollars to the cost of a mission. Trips in interplanetary space, however, expose the crew to heavy high-energy particles from cosmic rays (HZE particles), which have a high linear energy transfer. This high energy leads to significant biological damage (e.g. chromosomal aberrations, cancer induction). A recent report from the Committee on Space Biology and Medicine notes that only one systematic study of cancer induction from high-energy particles has been conducted (using the mouse Harderian gland). Predictions of cancer risk and acceptable radiation exposure in space are extrapolated from minimal data. Other areas of physiology also present problems, such as muscle loss, cardiovascular deconditioning, and vestibular adaptation. Despite all the issues, however, a focussed, aggressive research program that uses the resources of the International Space Station should pave the way for mankind's greatest adventure--a trip to Mars.

Humans↗

PubMed1992

Development of countermeasures for medical problems encountered in space flight.

By the turn of this century, long-duration space missions, either in low Earth orbit or for got early planetary missions, will become commonplace. From the physiological standpoint, exposure to the weightless environment results in changes in body function, some of which are adaptive in nature and some of which can be life threatening. Important issues such as environmental health, radiation protection, physical deconditioning, and bone and muscle loss are of concern to life scientists and mission designers. Physical conditioning techniques such as exercise are not sufficient to protect future space travellers. A review of past experience with piloted missions has shown that gradual breakdown in bone and muscle tissue, together with fluid losses, despite a vigorous exercise regimen can ultimately lead to increased evidence of renal stones, musculoskeletal injuries, and bone fractures. Biological effects of radiation can, over long periods of time increase the risk of cancer development. Today, a vigorous program of study on the means to provide a complex exercise regimen to the antigravity muscles and skeleton is under study. Additional evaluation of artificial gravity as a mechanism to counteract bone and muscle deconditioning and cardiovascular asthenia is under study. New radiation methods are being developed. This paper will deal with the results of these studies.

Aerospace Medicine↗

PubMed2001

Research activities at the Loma Linda University and Proton Treatment Facility--an overview.

The Loma Linda University (LLU) Radiobiology Program coordinates basic research and proton beam service activities for the university and extramural communities. The current focus of the program is on the biological and physical properties of protons and the operation of radiobiology facilities for NASA-sponsored projects. The current accelerator, supporting facilities and operations are described along with a brief review of extramural research projects supported by the program. These include space craft electronic parts and shielding testing as well as tumorigenesis and animal behavior experiments. An overview of research projects currently underway at LLU is also described. These include: 1) acute responses of the C57Bl/6 mouse immune system, 2) modulation of gene expression in the nematode C. elegans and rat thyroid cells, 3) quantitation of dose tolerance in rat CNS microvasculature, 4) behavioral screening of whole body proton and iron ion-irradiated C57Bl/6 mice, and 5) investigation of the role of cell integration into epithelial structures on responses to radiation.

Animals↗

PubMed2002

How do we get from cell and animal data to risks for humans from space radiations?

After four decades of human exploration in space, many scientists consider the medical consequences from radiation exposures to be the major biological risk associated with long-term missions. This conclusion is based upon results from a research program that has evolved over the past thirty years. Despite the diversity in both opinions and approaches that necessarily arise in research endeavors such as this, a commonality has emerged from our community. We need epidemiological data for humans, animal data in areas where no human data exist, and data on mechanisms to get from animal to humans. We need a programmatic infrastructure that addresses specific goals as well as basic research. These concepts might be deemed overly simplistic and even tautologous were it not for the fact that they are frequently underutilized and even ignored. This article examines the goals, premises, and infrastructures proposed by expert panels and agencies to address radiation risks in space. It is proposed that the required level of effort and the resources available demand a unified, focused international effort that is, at the same time, subjected to rigorous peer review if it is to be successful. There is a plan; let us implement it.

Animals↗

PubMed1990

Medical considerations for extending human presence in space.

The prospects for extending the length of time that humans can safely remain in space depend partly on resolution of a number of medical issues. Physiologic effects of weightlessness that may affect health during flight include loss of body fluid, functional alterations in the cardiovascular system, loss of red blood cells and bone mineral, compromised immune system function, and neurosensory disturbances. Some of the physiologic adaptations to weightlessness contribute to difficulties with readaptation to Earth's gravity. These include cardiovascular deconditioning and loss of body fluids and electrolytes; red blood cell mass; muscle mass, strength, and endurance; and bone mineral. Potentially harmful factors in space flight that are not related to weightlessness include radiation, altered circadian rhythms and rest/work cycles, and the closed, isolated environment of the spacecraft. There is no evidence that space flight has long-term effects on humans, except that bone mass lost during flight may not be replaced, and radiation damage is cumulative. However, the number of people who have spent several months or longer in space is still small. Only carefully-planned experiments in space preceded by thorough ground-based studies can provide the information needed to increase the amount of time humans can safely spend in space.

Adaptation, Physiological↗

PubMed2002

Advances in space radiation shielding codes.

Early space radiation shield code development relied on Monte Carlo methods and made important contributions to the space program. Monte Carlo methods have resorted to restricted one-dimensional problems leading to imperfect representation of appropriate boundary conditions. Even so, intensive computational requirements resulted and shield evaluation was made near the end of the design process. Resolving shielding issues usually had a negative impact on the design. Improved spacecraft shield design requires early entry of radiation constraints into the design process to maximize performance and minimize costs. As a result, we have been investigating high-speed computational procedures to allow shield analysis from the preliminary concept to the final design. For the last few decades, we have pursued deterministic solutions of the Boltzmann equation allowing field mapping within the International Space Station (ISS) in tens of minutes using standard Finite Element Method (FEM) geometry common to engineering design methods. A single ray trace in such geometry requires 14 milliseconds and limits application of Monte Carlo methods to such engineering models. A potential means of improving the Monte Carlo efficiency in coupling to spacecraft geometry is given.

Cosmic Radiation↗

PubMed2004

Radiation analysis for manned missions to the Jupiter system.

An analysis for manned missions targeted to the Jovian system has been performed in the framework of the NASA RASC (Revolutionary Aerospace Systems Concepts) program on Human Exploration beyond Mars. The missions were targeted to the Jupiter satellite Callisto. The mission analysis has been divided into three main phases, namely the interplanetary cruise, the Jupiter orbital insertion, and the surface landing and exploration phases. The interplanetary phase is based on departure from the Earth-Moon L1 point. Interplanetary trajectories based on the use of different propulsion systems have been considered, with resulting overall cruise phase duration varying between two and five years. The Jupiter-approach and the orbital insertion trajectories are considered in detail, with the spacecraft crossing the Jupiter radiation belts and staying around the landing target. In the surface exploration phase the stay on the Callisto surface is considered. The satellite surface composition has been modeled based on the most recent results from the GALILEO spacecraft. In the transport computations the surface backscattering has been duly taken into account. Particle transport has been performed with the HZETRN heavy ion code for hadrons and with an in-house developed transport code for electrons and bremsstrahlung photons. The obtained doses have been compared to dose exposure limits.

Cosmic Radiation↗

PubMed1996

Intercomparison of radiation measurements on STS-63.

A joint NASA Russia study of the radiation environment inside the Space Shuttle was performed on STS-63. This was the second flight under the Shuttle-Mir Science Program (Phase 1). The Shuttle was launched on 2 February 1995, in a 51.65 degrees inclination orbit and landed at Kennedy Space Center on 11 February 1995, for a total flight duration of 8.27 days. The Shuttle carried a complement of both passive and active detectors distributed throughout the Shuttle volume. The crew exposure varied from 1962 to 2790 microGy with an average of 2265.8 microGy or 273.98 microGy/day. Crew exposures varied by a factor of 1.4, which is higher than usual for STS mission. The flight altitude varied from 314 to 395 km and provided a unique opportunity to obtain dose variation with altitude. Measurements of the average east-west dose variation were made using two active solid state detectors. The dose rate in the Spacehab locker, measured using a tissue equivalent proportional counter (TEPC), was 413.3 microGy/day, consistent with measurements made using thermoluminescent detectors (TLDs) in the same locker. The average quality factor was 2.33, and although it was higher than model calculations, it was consistent with values derived from high temperature peaks in TLDs. The dose rate due to galactic cosmic radiation was 110.6 microGy/day and agreed with model calculations. The dose rate from trapped particles was 302.7 microGy/day, nearly a factor of 2 lower than the prediction of the AP8 model. The neutrons in the intermediate energy range of 1-20 MeV contributed 13 microGy/day and 156 microSv/day, respectively. Analysis of data from the charged particle spectrometer has not yet been completed.

Atlantic Ocean↗

PubMed1994

Single track effects, Biostack and risk assessment.

The scientific career of Prof. Bucker has spanned a very exciting period in the fledgling science of Space Radiation Biology. The capability for placing biological objects in space was developed, and the methods for properly packaging, retrieving and analyzing them were worked out. Meaningful results on the effects of radiation were obtained for the first time. In fact, many of the successful techniques and methodologies for handling biological samples were developed in Prof. Bucker's laboratories, as attested by the extensive Biostack program. He was the first to suggest and successfully carry out experiments in space directly aimed at measuring effects of single tracks of high-energy heavy galactic cosmic rays by specifically identifying whether or not the object had been hit by a heavy particle track. Because the "hit" frequencies of heavy galactic cosmic rays to cell nuclei in the bodies of space travelers will be low, it is expected that any effects to humans on the cellular level will be dominated by single-track cell traversals. This includes the most important generally recognized late effect of space radiation exposure: radiation-induced cancer. This paper addresses the single-track nature of the space radiation environment, and points out the importance of single "hits" in the evaluation of radiation risk for long-term missions occurring outside the earth's magnetic field. A short review is made of biological objects found to show increased effects when "hit" by a single heavy charged-particle in space. A brief discussion is given of the most provocative results from the bacterial spore Bacillus subtilis: experimental evidence that tracks can affect biological systems at much larger distances from the trajectory than previously suspected, and that the resultant inactivation cross section in space calculated for this system is very large. When taken at face value, the implication of these results, when compared to those from experiments performed at ground-based accelerators with beams at low energies in the same LET range, is that high-energy particles can exert their influence a surprising distance from their trajectory and the inactivation cross sections are some 20 times larger than expected. Clearly, beams from high-energy heavy-ion accelerators should be used to confirm these results. For those end points that can also be caused by low-LET beams such as high-energy protons, it is important to measure their action cross sections as well. The ratio of the cross sections for a high-LET beam to that of a low-LET beam is an interesting experimental ratio and, we suggest, of more intrinsic interest than the RBE (Relative Biological Effectiveness). It is a measure of the "biological" importance of one particle type relative to another particle type. This ratio will be introduced and given the name RPPE (Relative Per Particle Effectiveness). Values of RPPE have appeared in the literature and will be discussed. A rather well-known value of this quantity (13,520) has been suggested for the RPPE of high-energy iron ions to high-energy protons. This value was suggested by Letaw et al. Nature 330, 709-710 (1987)] we will call it the Letaw limit. It will be discussed in terms of the importance of the heavy-ion component vs light-ion component of the galactic cosmic rays. It is also pointed out, however, that there may be unique effects from single tracks of heavy ions that do not occur from light-ion tracks. For such effects, the concepts of both RBE and RPPE lose their meaning.

Bacillus subtilis↗