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Biomedical subjects

E H Goodwin

Publications and source records attributed to E H Goodwin.

25 records · Page 2Linked to original sources
PubMed1994

RBE: mechanisms inferred from cytogenetics.

Cyclotron-accelerated heavy ion beams provide a fine degree of control over the physical parameters of radiation. Cytogenetics affords a view into the irradiated cell at the resolution of chromosomes. Combined they form a powerful means to probe the mechanisms of RBE. Cytogenetic studies with high energy heavy ion beams reveal three LET-dependent trends for 1) level of initial damage, 2) distribution of damage among cells, and 3) lesion severity. The number of initial breaks per unit dose increases from a low-LET plateau to a peak at approximately 180 keV/micrometer and declines thereafter. Overdispersion of breaks is significant above approximately 100 keV/micrometer. Lesion severity, indicated by the level of chromosomal fragments that have not restituted even after long repair times, increases with LET. Similar studies with very low energy 238Pu alpha particles (120 keV/micrometer) reveal higher levels of initial breakage per unit dose, fewer residual fragments and a higher level of misrepair when compared to high energy heavy ions at the same LET. These observations would suggest that track structure is an important factor in genetic damage in addition to LET.

Alpha Particles↗
PubMed1994

Chromosomal damage and repair in G1-phase Chinese hamster ovary cells exposed to charged-particle beams.

Chromosomal fragmentation was examined in G1-phase Chinese hamster ovary cells using the premature chromosome condensation (PCC) technique. The yield and distribution of chromatin breaks, the lesions revealed by PCC, were measured in cells exposed to X rays or each of nine particle beams covering a range of LET from 0.56 to 2700 keV/microns. The average number of breaks per cell was found to be linearly proportional to the fluence of high-LET neon ions (183 keV/microns). Assuming a linear response for the other beams, the level of breakage per unit dose rose from a plateau at the lowest LET values to a peak in the 100-200 keV/microns range and then declined continuously thereafter, eventually falling well below the low-LET plateau. The maximum breakage RBE was 1.5. The average number of breaks per particle traversal rose steadily from 0.006 to 11 breaks/cell as the LET increased from 0.56 to 2700 keV/microns. The breaks were distributed randomly within the cell population after low-LET irradiation, but became progressively over-dispersed with increasing LET. Rejoining of prematurely condensed chromosomes plus fragments was followed for up to 5 h for four particle beams having LET values between 0.56 and 183 keV/microns. An LET-dependent trend toward higher levels of residual fragments was observed.

Animals↗
PubMed1992

Heavy ion-induced chromosomal damage and repair.

We have been using the "premature chromosome condensation (PCC)" technique to investigate chromosomal breakage, rejoining and misrepair induced by accelerated heavy ions. With the presentation of new Fe experiments, we now review the available PCC data to summarize our current understanding of the action of high velocity charged particles on mammalian chromosomes. Implications for the survival RBE/LET relationship are also discussed.

Animals↗
PubMed1991

Transmission of radiation-induced acentric chromosomal fragments to micronuclei in normal human fibroblasts.

A simplifying assumption made when calculating the probability of a chromosomal aberration resulting in a micronucleus is that virtually all radiation-induced micronuclei result from acentric fragments. In the present study we used antibodies to chromosomal centromeres (kinetochores) to determine the frequency of centric versus acentric micronuclei in normal human fibroblasts exposed to 6 Gy of 60Co gamma rays while they were in density-inhibited growth. Up to 14% of the micronuclei induced by this exposure contained one or more kinetochores; i.e., they were not composed of acentric chromatin. By deleting kinetochore-positive micronuclei from the analysis, and by reconstructing micronucleus frequencies based on the fraction of cells that had divided following radiation exposure, a direct comparison between micronuclei and acentric chromosome fragments was made. On that basis, the probability of an acentric fragment becoming a visible micronucleus in either daughter cell of a dividing pair was estimated to be about 0.6. The distribution of acentric fragments among mitotic cells conformed to Poisson expectation, while the distribution of micronuclei among daughter cells was significantly overdispersed. The phenomenon of overdispersion is discussed in connection with proposed cellular processes that effect a nonrandom segregation of acentric fragments.

Centromere↗
PubMed1991

The dose-dependent fragmentation of chromatin in human fibroblasts by 3.5-MeV alpha particles from 238Pu: experimental and theoretical considerations pertaining to single-track effects.

The technique of premature chromosome condensation (PCC) was used to examine the dose-response relationship for the production of interphase (G0) chromosome fragments in noncycling normal human fibroblasts following exposure to 238Pu alpha particles, with special emphasis on the low-dose region. The dose response was convincingly linear from 0.2 to 3.0 Gy. Analysis of further data collected over a dose range of 1.1 to 22.4 cGy provided no evidence of deviation from linearity in this low-dose region. The fact that this lower dose range extends into the region where single-particle effects are dominant suggests that a linear extrapolation of this response from higher to lower doses is valid. Ratios of coefficients for the induction of fragments produced by 238Pu alpha particles versus 60Co gamma rays gave an RBE of 2.34 +/- 0.09. Distributions of fragments among 60Co gamma-irradiated cells were consistent with a Poisson expectation of random damage. In contrast, overdispersion appeared to be a general feature of 238Pu alpha-particle-induced fragmentation, a phenomenon explainable under the assumption that single-particle traversals are capable of producing multiple PCC fragments. Data obtained were used to estimate practical and theoretical lower-dose limits of detection of initial chromatin breaks provided by current PCC methodology.

Alpha Particles↗
PubMed1988

Cell-cycle dependence of X-ray oxygen effect: role of endogenous glutathione.

The oxygen effect was measured in human T-1 cell populations synchronized by mitotic selection and x-irradiated in vitro after they were allowed to progress to six different ages during the division cycle. Survival curves and dose-ratio calculations with 95% confidence intervals were obtained from computer fits of the data to the linear-quadratic model. The oxygen enhancement ratio (OER) values at the 1% survival increased level were 2.6 +/- 0.08 in G1/early S phase and increased to 3.0 +/- 0.15 in late S/G2 phase. The OER values at 10% survival increased linearly from 2.6 +/- 0.2 for G1-phase cells to 3.2 +/- 0.2 for late S/G2-phase cells. The increased OER in S-phase cells was the result of a greater hypoxic radioresistance compared with that measured with G1-phase cells. In parallel experiments with synchronized cell populations, glutathione (GSH) and glutathione disulfide levels were measured by the Tietze assay and also were found to increase over the same period. The molecular mechanisms responsible for the radiation response involve a number of factors, one of which in this cell line may be GSH levels, especially under conditions of hypoxic exposure. Our data are consistent with the hypothesis that G1- to late S-phase, age-dependent fluctuations in GSH content may be correlated with changes in OER during the human T-1 cell cycle. Changes in GSH content relative to its constitutive levels in the cell and alternative reductive factors (i.e., protein thiols), as well as their cellular location, may be important factors in the comparison of these findings to other cell lines.

Cell Cycle↗