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Lett, J. T.

Publications and source records attributed to Lett, J. T..

At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS1999

Late ophthalmological complications after total body irradiation in non-human primates

PURPOSE: To investigate the long-term effects of total body irradiation (TBI) on the incidence and time course of ocular complications. MATERIALS AND METHODS: Rhesus monkeys treated with TBI photon doses up to 8.5 Gy and proton doses up to 7.5 Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. RESULTS: Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photon-doses of 8 and 8.5 Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. CONCLUSIONS: Radiation alone for doses up to 8.5 Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5 Gy and proton doses in excess of 2.5 Gy.

NASA Discipline Radiation Health↗
NASA NTRS1996

Damage to the photoreceptor cells of the rabbit retina from 56Fe ions: effect of age at exposure, 1

Optic and proximate tissues of New Zealand white (NZW) rabbits at ages (approximately 3.5 years) near the middle of their median lifespan (5-7 years) were given 0.5-3.5 Gy of 465 MeV u-1 56Fe ions in the Bragg plateau region of energy deposition at a linear energy transfer (LET infinity) of 220 +/- 31 keV micrometer-1. Dose-dependent losses of retinal photoreceptor cells (rods) occurred until 1-2 years after irradiation, the period of this interim report. Similar cumulative losses of photoreceptor cells were seen during the period 1-2 years post-irradiation for rabbits given comparable exposures when young (6-9 weeks old). Since losses of photoreceptor cells at early times had not been determined previously, the current experiment, which was designed to simulate the responses of mature astronauts, redressed that deficiency.

NASA Program NSCORT↗
NASA NTRS1996

Experimental models for cellular radiation targets: LET, RBE and radioprotectors

The topics of this presentation are: a brief review of the early research, the ideas it stimulated and the ways they are used in current efforts to explain cellular radiosensitivity; an analysis of the strengths and weaknesses of two experimental models used in vitro for simulating the induction of double strand breaks (DSB) and single strand breaks (SSB) in situ. Note that when alkali is used to denature cellular DNA for the determination of strand breaks, both overt SSB and the SSB that result from DSB in the denaturation process are recorded as total strand breaks (TSB). All information is taken from published literature.

NASA Discipline Number 93-10↗
NASA NTRS1994

Effects of Ar-40 and Fe-56 ions on retinal photoreceptor cells of the rabbit: Implications for manned missions to Mars

Losses of photoreceptor cells (rods) from the retinas of New Zealand white (NZW) rabbits were detectable within 2 years after localized acute irradiation of optic and proximal tissues with greater than or equal to 7 Gy of 530 MeV u(exp -1) Ar-40 ions or greater than or equal to 2 Gy of 465 MeV u(exp -1) Fe-56 ions in the Bragg plateau region of energy deposition. Those limits were determined only from an analysis of variance of dose groups because the shapes of the dose response curves at early post-irradiation times are not known, a concern being addressed by experiments in progress. Losses of photoreceptor cells for the period 0.5-2.5 years post-irradiation, determined by provisional linear regression analysis, were approxiamtely 1.7% Gy(exp -1) and 2.5% Gy(exp.-1) for Ar-40 and Fe-56 ions, respectively.

Williams, G. R.↗
NASA NTRS1994

Helium-ion-induced human cataractogenesis

Retrospective and ongoing analyses of clinical records from 347 primary intraocular melanoman patients treated with helium ions at Lawrence Berkeley Laboratory (LBL) will allow examination of the exposure-response data for human cataract; which is a complication of the therapy from incidental exposure of the lens. Direct particle beam traversal of at least a portion of the lens usually is unavoidable in treatment of posterior intraocular tumors. The precise treatment planned for each patient permits quantitative assessment of the lenticular dose and its radiation quality. We are reporting our preliminary results on the development of helium-ion-induced lens opacifications and cataracts in 54 of these patients who had 10% or less of their lens in the treatment field. We believe these studies will be relevant to estimating the human risk for cataract in space flight.

Blakely, E. A.↗
NASA NTRS1994

Effects of 40Ar and 56Fe ions on retinal photoreceptor cells of the rabbit: implications for manned missions to Mars

Losses of photoreceptor cells (rods) from the retinas of New Zealand white (NZW) rabbits were detectable within 2 years after localized acute irradiation of optic and proximal tissues with > or = 7 Gy of 530 MeV u-1 40Ar ions or > or = 2 Gy of 465 MeV u-1 56Fe ions in the Bragg plateau region of energy deposition. Those limits were determined only from an analysis of variance of dose groups because the shapes of the dose response curves at early post-irradiation times are not known, a concern being addressed by experiments in progress. Losses of photoreceptor cells for the period 0.5-2.5 years post-irradiation, determined by provisional linear regression analysis, were approximately 1.7% Gy-1 and 2.5% Gy-1 for 40Ar and 56Fe ions, respectively.

NASA Discipline Radiation Health↗
NASA NTRS1992

Deoxyribonucleoprotein structure and radiation injury - Cellular radiosensitivity is determined by LET-infinity-dependent DNA damage in hydrated deoxyribonucleoproteins and the extent of its repair

Until recently, OH radicals formed in bulk nuclear water were believed to be the major causes of DNA damage that results in cell death, especially for sparsely ionizing radiations. That hypothesis has now been challenged, if not refuted. Lethal genomic DNA damage is determined mainly by energy deposition in deoxyribonucleoproteins, and their hydration shells, and charge (energy) transfer processes within those structures.

Lett, J. T.↗
NASA NTRS1992

Late cataractogenesis in primates and lagomorphs after exposure to particulate radiations

Results are presented from a study in which regular examinations of cataractogenic development were conducted since 1987 in monkeys that were exposed in 1969, at the age of about 2 years, to low doses of 'mixed-energy' protons (10 and 110 MeV). The results of comparisons with age-matched controls showed that the cataractogenic patterns observed in the exposed monkeys are consistent with those observed in other groups of monkeys that were exposed at similar ages in 1964 and 1965 to protons of different energies (Lett et al., 1986, 1988, 1989, and 1991). Comparisons were also made among recent results from different groups of primates and from New Zealand white rabbits that were exposed when young to Fe-56 and were monitored continuously thereafter.

Cox, A. B.↗
NASA NTRS1992

Damage to cellular DNA from particulate radiations, the efficacy of its processing and the radiosensitivity of mammalian cells. Emphasis on DNA double strand breaks and chromatin breaks

For several years, it has been evident that cellular radiation biology is in a necessary period of consolidation and transition (Lett 1987, 1990; Lett et al. 1986, 1987). Both changes are moving apace, and have been stimulated by studies with heavy charged particles. From the standpoint of radiation chemistry, there is now a consensus of opinion that the DNA hydration shell must be distinguished from bulk water in the cell nucleus and treated as an integral part of DNA (chromatin) (Lett 1987). Concomitantly, sentiment is strengthening for the abandonment of the classical notions of "direct" and "indirect" action (Fielden and O'Neill 1991; O'Neill 1991; O'Neill et al. 1991; Schulte-Frohlinde and Bothe 1991 and references therein). A layer of water molecules outside, or in the outer edge of, the DNA (chromatin) hydration shell influences cellular radiosensitivity in ways not fully understood. Charge and energy transfer processes facilitated by, or involving, DNA hydration must be considered in rigorous theories of radiation action on cells. The induction and processing of double stand breaks (DSBs) in DNA (chromatin) seem to be the predominant determinants of the radiotoxicity of normally radioresistant mammalian cells, the survival curves of which reflect the patterns of damage induced and the damage present after processing ceases, and can be modelled in formal terms by the use of reaction (enzyme) kinetics. Incongruities such as sublethal damage are neither scientifically sound nor relevant to cellular radiation biology (Calkins 1991; Lett 1990; Lett et al. 1987a). Increases in linear energy transfer (LET infinity) up to 100-200 keV micron-1 cause increases in the extents of neighboring chemical and physical damage in DNA denoted by the general term DSB. Those changes are accompanied by decreasing abilities of cells normally radioresistant to sparsely ionizing radiations to process DSBs in DNA and chromatin and to recover from radiation exposure, so they make significant contributions to the relative biological effectiveness (RBE) of a given radiation.(ABSTRACT TRUNCATED AT 400 WORDS).

Non-NASA Center↗
NASA NTRS1991

A study of lens opacification for a Mars mission

A method based on risk-related cross sections is used to estimate risks of 'stationary' cataracts caused by radiation exposures during extended missions in deep space. Estimates of the even more important risk of late degenerative cataractogenesis are made on the basis of the limited data available. Data on lenticular opacification in the New Zealand white rabbit, an animal model from which such results can be extrapolated to humans, are analyzed by the Langley cosmic ray shielding code (HZETRN) to generate estimates of stationary cataract formation resulting from a Mars mission. The effects of the composition of shielding material and the relationship between risk and LET are given, and the effects of target fragmentation on the risk coefficients are evaluated explicitly.

Shinn, J. L.↗
NASA NTRS1989

The role of repair in the survival of mammalian cells from heavy ion irradiation - Approximation to the ideal case of target theory

Experiments are discussed in which the cell-cycle dependency of the repair deficiency of the S/S variant of the L5178Y murine leukemic lymphoblast was examined by treatment with the heavy ions, Ne-20, Si-28, Ar-40, Fe-56, and Nb-93. Evidence from those studies provide support for the notion that as the linear energy transfer of the incident radiation increases the ability of the S/S cell to repair radiation damage decreases until it is eliminated around 500 keV/micron. In the region of the latter linear energy transfer value, the behavior of the S/S cell approximates the ideal case of target theory where post-irradiation metabolism does not influence cell survival.

Lett, J. T.↗
NASA NTRS1989

Late cataractogenesis caused by particulate radiations and photons in long-lived mammalian species

Radiation cataractogenesis induced by small acute doses of particulate radiations and photons in the New Zealand white rabbit (Oryctolagus cuniculus), the beagle dog (Canis familiaris) and the rhesus monkey (Macaca mulatta) is discussed in the context of the use of animal models to assess the radiation hazards faced by humans during lengthy sojourns in deep space. Attention is paid to (1) the importance of lifespan studies with long-lived species - the above animals have median lifespans in captivity of 5-7, 13-14 and 25 years, respectively; and (2) the magnitudes of possible dose thresholds for cataractogenesis from sparsely ionizing radiations and the modifications of those thresholds by the late degenerative phase of the phenomenon.

Lett, J. T.↗
NASA NTRS1988

Age dependency of base modification in rabbit liver DNA

Age-related modifications of DNA bases have been observed in the liver of the New Zealand white (NZW) rabbit (Oryctolagus cuniculus), a lagomorph with a median life span in captivity of 5-7 yr. The ages of the animals studied ranged from 6 wk to 9 yr. After the DNA had been extracted from the liver cell nuclei and hydrolyzed with acid, the bases were analyzed by column chromatography with Cellulofine gels (GC-15-m). Two peaks in the chromatogram, which eluted before the four DNA bases, contained modified bases. Those materials, which were obtained in relatively large amounts from old animals, were highly fluorescent, and were shown to be crosslinked base products by mass spectrometry. The yield of crosslinked products versus rabbit age (greater than 0.5 yr) can be fitted by an exponential function (correlation coefficient: 0.76 +/- 0.09).

NASA Discipline Radiation Health↗
NASA NTRS1986

Cataractogenic potential of ionizing radiations in animal models that simulate man

Aspects of experiments on radiation-induced lenticular opacification during the life spans of two animal models, the New Zealand white rabbit and the rhesus monkey, are compared and contrasted with published results from a life-span study of another animal model, the beagle dog, and the most recent data from the ongoing study of the survivors from radiation exposure at Hiroshima and Nagasaki. An important connection among the three animal studies is that all the measurements of cataract indices were made by one of the authors (Lee), so variation from personal subjectivity was reduced to a minimum. The primary objective of the rabbit experiments (radiations involved: Fe-56, Ar-40, and Ne-20 ions and Co-60 gamma photons) is an evaluation of hazards to astronauts from Galactic particulate radiations. An analogous evaluation of hazards from solar flares during space flight is being made with monkeys exposed to 32, 55, 138 and 400-MeV protons. Conclusions are drawn about the proper use of animal models to simulate radiation responses in man and the levels of radiation-induced lenticular opacification that pose risks to man in space.

Lett, J. T.↗
NASA NTRS1984

Late effects from particulate radiations in primate and rabbit tissues

In connection with studies regarding the hazards posed by ionizing radiations to man in space, the U.S. Air Force conducted an experiment about 20 years ago. In this experiment a large number of young rhesus monkeys was exposed to proton fluxes similar to those to be anticipated during solar flares. After irradiation, the animals were kept at the USAF School of Aerospace Medicine in Texas. The monkeys have been employed in investigations concerning aspects of late radiation damage. These investigations are discussed, taking into account the propagation of fibroblasts from irradiated monkeys. The results of the investigations are evaluated, giving attention also to experiments with white rabbits. It is found that, except in the case of major solar flares, when acute radiation damage could lead quickly to death, the hazards to astronauts from space radiations arise from such debilitating late effects as cataracts, damage to the central nervous system and benign tumors, and life-threatening neoplasia.

Lett, J. T.↗
NASA NTRS1983

Cataractogenesis from high-LET radiation and the Casarett model

The long-term effects on specific animal tissues of exposure to heavy ion irradiation are studied in experiments on cataractogenesis in mice and rabbits. Five groups of rabbits at ages from 8 weeks to 5.3 years were irradiated to a dose of 9.0 Gy of Bragg plateau Ne-20 ions, while mice were exposed to single and total fractionated doses of 4.17 Gy gamma rays or 0.40 to 1.20 Gy of C-12, Ne-20 or Ar-40 particles. Measurements of lens opacities over time show that in the year since irradiation, cataractogenesis is delayed and less severe in rabbits irradiated at age 6 months compared to younger animals, although it is possible that the late effects in adults will surpass those found in the young. The fractionation of the total dose of gamma rays in mice is observed to lead to a marked reduction in the extent of lens opacity after one year, while fractionated heavy ion doses caused a greater degree of posterior lens opacification. Evaluations of the effects of the LET of different ions on cataractogenesis are consistent with RBEs of about 5, 3 and 1-2 for Ar-40, Ne-20 and C-12 ions, respectively. Results thus support the Casarett model of radiation damaging stem cell populations that are not necessarily part of the vasculature.

Cox, A. B.↗
NASA NTRS1983

Late skin damage in rabbits and monkeys after exposure to particulate radiations

Preliminary results are reported of experiments on the late effects of exposure to particulate radiations on stem cell populations. Skin biopsies were taken from the ears of rabbits irradiated 2-5 years previously with 530 MeV/amu Ar ions (LET 90 keV/micron), or 365 MeV/amu Ne ions (LET 35 keV micron), and from the chests and inner thighs of rhesus monkeys irradiated 16-18 years previously with 32-MeV protons (LET about 1.2 keV/micron). Skin fibroblast cultures obtained from the biopsy samples in rabbits were observed to undergo dose-dependent decreases in in vitro life span, with estimated survival curves showing the effects of Ar-ion irradiation to be more severe than those of Ne-ion irradiation. In addition, the healing of the biopsy wound was observed to become slower as radiation dose increased. In the monkey, radiation reduced the average number of fibroblasts at the time of cessation of growth in culture. Results thus demonstrate the capacity of skin sampling to reveal stem cell destruction, and have important implications for astronauts and other persons at risk of particle exposure with regard to healing responses to trauma or surgery.

Bergtold, D. S.↗