In Vivo Restitution of the DNA Structure in Gamma Irradiated Rabbit Retinas

Wheeler, Kenneth T.; Sheridan, Robert E.; Pautler, E.L.; Lett, J. T.

doi:10.2307/3573774

Cited by 47 publications

(12 citation statements)

References 15 publications

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“…3 were chosen to illustrate the maximum differences among the preparations. For completeness, we can also add that similar results were obtained from preparations of photoreceptor cells following in situ irradiation of rabbit retinas (14,15). So the FMF studies demonstrated that the cerebellar neurons were not stimulated to undergo detectable (>10%) DNA replication in our experiments and that extents of replication exceeding that figure were not required for the reconstruction of rapidly sedimenting DNA species.…”

Section: Resultssupporting

confidence: 78%

“…As in a number of other situations (7,8,15) 90 min and more rapidly sedimenting components do not appear until several hours later. In terms of the working model of mammalian DNA structure, these results would be interpreted as rejoining of strand breaks to reconstitute the subunits followed by restoration of the chromosomal DNA structure.…”

Section: Resultssupporting

confidence: 66%

“…All the above procedures have been fully documented (13,(17)(18)(19)(20). Radioactively-labeled DNA markers obtained from Chinese hamster ovary cells which had been exposed to 1 krad of x-rays (14,15,21) were employed in all sedimentation runs with the DNA from animals older than 2 years. RESULTS Sedimentation.…”

Section: Methodsmentioning

confidence: 99%

“…One of these mechanisms rejoins the strand breaks within DNA molecules thought to represent chromosomal subunits (7)(8)(9); the other restores the DNA structure found in the unirradiated cell (7,8,(10)(11)(12)(13). Since non-dividing cells, as exemplified by the retinal photoreceptor cells of the rabbit (14,15) and the internal granular-layer neurons of the young beagle (13), also exhibit analogous repair mechanisms, a general rule could be that all normal mammalian cells possess such capacities. Exceptions to this rule, expressed as a loss of the ability to repair disruptions in the DNA structure, could then occur under certain special conditions.…”

mentioning

confidence: 99%

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On the Possibility That DNA Repair Is Related to Age in Non-Dividing Cells

Wheeler

Lett

1974

Proc. Natl. Acad. Sci. U.S.A.

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Possible age-related deterioration in the efficacy of DNA repair was investigated in a complement of non-dividing mammalian cells which is not replenished during the lifetime of the animal. Internal granular-layer neurons were extracted from the cerebella of beagle dogs, aged from 7 weeks to 13 years, following exposure in situ to 4700 rads of collimated aCo gamma rays. The alkaline sucrose-gradient sedimentation profiles obtained from the DNA of those neurons after various post-irradiation periods in situ can be interpreted: (a) that there is not an age-associated decrease in the ability of the cells to rejoin the single-strand breaks induced by radiation, but (b) that there may be an age-associated decline in the size of the DNA-containing species which can be extracted from unirradiated cells. The latter effect may reflect normal aging of the cerebellum.Despite outward differences, a majority of the current theories of aging rest upon the assumption that modification of genetic material is an essential factor in the aging process. There have been indications that structural alterations in mammalian chromatin, such as chromosomal aberrations (1-3) and ruptures of DNA strands (4,5) accumulate with age in cell populations which usually undergo limited proliferation in situ. Both phenomena may represent expression of unrepaired DNA damage.We believe that the repair of x-ray induced breaks in the DNA structure of mammalian cells in proliferative culture may be interpreted in terms of two generalized rejoining mechanisms (6-8). One of these mechanisms rejoins the strand breaks within DNA molecules thought to represent chromosomal subunits (7-9); the other restores the DNA structure found in the unirradiated cell (7,8,(10)(11)(12)(13) We chose to explore the third possibility with the internal granular-layer neurons of the cerebellum of the beagle because those neurons appear as a fully differentiated population of non-dividing cells at the birth of the animal (or very shortly thereafter) and are not replenished during its lifetime. The primary analytical approach explored the rejoining of DNA strand breaks, produced in situ by a single dose of ionizing radiation, as a function of age. The use of a single yv-ray dose was imposed by the complexity of the rejoining mechanisms which effectively contracted even a colony of a hundred beagles into a limited supply of animals of suitable ages. Similar considerations motivated the distribution of animals among control and experimental groups. The magnitude of the chosen y-ray dose reflected detailed experiments with 7 week-old pups (13) which provide the base line for the present study. METHODS AND MATERIALSCerebella of some hundred beagle dogst, aged from 7 weeks to 13 years, were irradiated in situ with 4700 rads of collimated 60Co y-rays from an Eldorado 8 teletherapy unit. Source decay imposed a 20% decline in dose rate from 235 rads/min during the experiments. At a suitable post-irradiation interval an animal was sacrificed, the cerebellum was removed, the inte...

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Section: Resultssupporting

confidence: 78%

Section: Resultssupporting

confidence: 66%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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On the Possibility That DNA Repair Is Related to Age in Non-Dividing Cells

Wheeler

Lett

1974

Proc. Natl. Acad. Sci. U.S.A.

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“…Then the ERG is lost permanently within a few hours (Baily and Noell 1958, Wheeler, Pautler and Lett 1972, Wheeler, Sheridan, Pautler and Lett 1973 and the rejoining of DNA strand breaks in the nuclei of the photoreceptor (rod) cells is both limited and transitory (Wheeler et al 1972, Wheeler et al . 1973) .…”

Section: Introductionmentioning

confidence: 97%

Effects of Heavy Ions on Rabbit Tissues: Loss of Electroretinogram and DNA Repair in Retinal Photoreceptor Cells

Keng

Lett

1981

International Journal of Radiation Biology and Related Studies

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Optic and proximate tissues of New Zealand white rabbits were exposed to the Bragg plateau regions of 530 MeV/amu Ar ions and 365 MeV/amu Ne ions and also to 60Co gamma rays. The linear energy transfers (LET infinity s) for the radiations were 90 +/- 5, 35 +/- 3 and 0.3 keV/micrometer, respectively. Single acute exposures to all three radiations caused only limited changes in the electroretinogram (ERG) until a critical dose was approached. At that dose, which was 45 +/- 3 Gy for all three types of radiation, a sudden loss in the b-wave of the ERG occurred. From less accurate measurements, it appeared that the response of the a-wave of the ERG was similar. The critical dose for ERG loss was reflected also in the rejoining of strand breaks in the DNA of retinal photoreceptor cells. Above the critical dose, the rejoining of DNA strand breaks was limited; below the critical dose, the rejoining of DNA strand breaks approached completion even though it took days to do so. In the latter respect, the response of photoreceptor cells to heavy-ion irradiation in situ is different from that reported for proliferating cells in culture.

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