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Biomedical subjects

M Zaider

Publications and source records attributed to M Zaider.

At least 91 records · Page 5Linked to original sources
PubMed1988

Low-dose rate irradiation.

There are a number of rather obvious conclusions from these experimental data that have implications in clinical radiotherapy: (1) Survival curves for cells of human origin, in general, have a smaller initial shoulder and exhibit greater sensitivity to ionizing radiation than cells of rodent origin. (2) Nevertheless, the response of human cells to gamma-rays, in a fractionated or low-dose schedule, is dominated by repair. (3) Radiosensitivity, as well as the repair of sublethal damage as evidenced by the dose rate effect, is very similar for a range of normal human cells, including skin and lung fibroblasts, as well as endothelial cells from umbilical cord veins. (4) Human tumor cells are much more variable than normal cells in radiosensitivity, and in the repair of sublethal damage, evident in the dose rate effect. Some show a smaller, and some show a larger dose rate effect than normal cells. (5) Consequently, the use of a large number of fractions, as for example in hyperfractionation regimens, is contraindicated in those tumors that show repair factors larger than for normal tissues; though of course it is a substantial advantage in other cases.

DNA Repair↗
PubMed1988

On the application of microdosimetry to radiobiology.

The pertinence of proportional counter microdosimetry to radiobiology rests on the idea of the site model; in view of the current emphasis on formalisms based on the distance model, it would appear that the role of experimental microdosimetry as a predictive tool is compromised. In this paper we challenge this opinion. It is shown that, to the extent that the site model is not only limited to convex sites of simple geometry, (a) the site model and the distance model become only complementary aspects (i.e., two possible interpretations) of the same formalism, and current biophysical theory is not equipped to discriminate, based on experimental evidence, between the two; (b) proportional counter microdosimetry retains its validity; and (c) for any cellular system [characterized by a function gamma(chi)] the ratio alpha/beta between the linear and quadratic components of the dose-response function can be calculated as a weighted sum of dose-averaged specific energies measured in a series of spherical sites (of different dimensions). An algorithm is provided for calculating the weighting factors.

Mathematics↗
PubMed1988

Radiation response characteristics of human cells in vitro.

Improvements in tissue culture techniques and growth media have made it possible to culture a range of cells of human origin, both normal and malignant. The most recent addition to the list are endothelial cells from umbilical cord veins. Interesting results in radiosensitivity studies of these human cells have been obtained, some of which may have implications in radiation therapy. (i) Repair of potentially lethal damage (PLDR) has been observed in all cell lines investigated; cells of normal origin repair PLD at least as well as malignant cells, which makes clinical trials of PLDR inhibitors of doubtful usefulness. (ii) No apparent correlation can be made between the extent of PLDR and the traditional radioresponsiveness of a particular tumor type. Indeed, if anything, it could appear to have an inverse correlation since the most resistant tumor cells show the smallest amount of PLD repair. (iii) Dose-rate effects appear to be better predictors of radiosensitivity than PLDR capacity. (iv) Sublethal damage repair, manifest by a dose-rate effect, has also been observed in all human cell lines tested. Cells of normal tissue origin, including fibroblasts and endothelial cells, exhibit a dose-rate effect that is intermediate between that for cells from traditionally resistant tumors (melanoma and osteosarcoma) and cells from more sensitive tumors (neuroblastoma and breast).

Cell Line↗
PubMed1987

Radiation repair in human endothelial cells.

Damage to blood vessels caused by ionizing radiation is considered to be an important dose limiting factor for late effects in many organs. However, the radiation response of the endothelial cells which line the vasculature has not been well-documented, particularly for human endothelial cells. In the present study, human endothelial cells were obtained from fresh umbilical cords and cultured in monolayer. Immunofluorescent staining of factor VIII antigen was used to verify the endothelial nature of the cultured cells. The cells were irradiated with Cs-137 rays (1.35 Gy/min) in plateau phase to determine radiation sensitivity and ability to repair potentially lethal damage (PLD) and sub-lethal damage (SLD). The endothelial cells demonstrated moderate radiosensitivity that varied slightly between different cords. As demonstrated by delayed plating experiments, PLD repair ability was substantial, with repair factors of 0.70-0.80. SLD repair capability, as demonstrated by split dose experiments, was relatively modest. A survival enhancement of 2.0-2.2, for example, was observed when 8 Gy single dose survival was compared to two 4 Gy doses. In terms of PLD and SLD repair as well as initial slope (alpha) the endothelial cells were similar to normal human lung and skin fibroblasts previously studied. Compared to malignant cell lines, PLD repair was generally larger whereas the initial slope (alpha) was intermediate-steeper than the radioresistant tumor types but shallower than the more sensitive tumor derived cells.

Cell Survival↗
PubMed1987

Potentially lethal damage repair in human cells.

Potentially lethal damage repair (PLDR) in human cells was investigated by delayed plating experiments with three malignant tumor cell lines (breast, colon and neuroblastoma) and two normal diploid lines (lung fibroblasts) in exponential and plateau phases. All cell lines demonstrated PLDR which was considerably higher for all the cell lines in plateau phase compared to log phase. At survival levels of 0.01, the two fibroblast lines had recovery ratios of 3.8 and 4.0 for 6 h delayed plating in plateau phase. The malignant lines showed recovery ratios of 5.7 (neuroblastoma), 3.2 (breast carcinoma) and 2.4 (colon carcinoma). The data were fitted to the linear quadratic equation and in addition, a repair factor was developed to compare survival for immediate and delayed plating: S(D) = exp[-gamma (alpha D + beta D2)] where gamma = 1 for immediate plating. Previously published data on human tumor and normal lines were also fitted to this equation. In all instances the three parameter equation (alpha, beta, gamma) allowed a good fit of the survival data for immediate and delayed plating. By using the same alpha, beta for the zero hour and 6 h survival curves, the gamma factor allows a much more useful method of comparing PLDR among different cell lines. The gamma factor for the two lung fibroblast lines were 0.70 and 0.71 while skin fibroblasts also had a 0.71 factor. The six malignant lines ranged from 0.62 to 0.93 with all but the neuroblastoma line having a higher factor (and therefore decreased PLDR capacity) than the normal lines. No correlation between PLDR and in vitro radiosensitivity or clinical radiosensitivity of the tumor type was found.

Cell Line↗
PubMed1987

Dose-rate effects in normal and malignant cells of human origin.

Human cell lines derived from normal tissue and malignant tumours were irradiated in plateau phase under acute (81 Gy/h) or protracted (0.1-0.7 Gy/h) exposure to determine initial survival curve slopes, assess sublethal damage repair (SLDR) capability, and establish differences in survival due to SLDR over a range of dose rates. No correlation was found between clinical resistance of the tumor types and initial slope or survival at 2 Gy. Sublethal damage repair was assessed by comparing survival curves for acute and continuous irradiation. All cell lines showed significant SLDR, with the more clinically resistant tumour types demonstrating the best recovery rates. The survival data also demonstrated little difference in cell killing over the 0.1-0.7 Gy/h range. Using a modified linear-quadratic model with provisions for SLDR, it was found that for these cell lines the repair half-time was less than 1 h, with no significant change in the amount of recovery from sublethal damage at dose rates below 1 Gy/h.

Cell Line↗
PubMed1987

Inactivation of synchronized mammalian cells with low-energy X rays--results and significance.

Results for inactivation of hydroxyurea-synchronized V-79 cells by ultrasoft aluminum characteristic X rays of energy 1.5 keV are presented. Limiting RBEs at low doses, relative to 137Cs gamma rays, of 1.8 and 6.4 are, respectively, found for cells at the G1/S and late S stages of the cell cycle. The late-S data are analyzed in the light of previous experiments carried out under similar conditions, also designed to probe the effects of energy deposition in nanometer-sized sites, in which cells were irradiated with correlated pairs of ions. Within the framework of the theory of dual radiation action, the results for ultrasoft X rays and gamma rays can be deduced solely from track simulations and the results of the high-LET molecular ion experiment.

Animals↗
PubMed1987

Cell survival and plating efficiency.

The question of whether cellular radiation sensitivity is independent or related to plating efficiency (PE) is addressed. Three different cell lines, one human and mortal (AG 1522), one rodent and immortal (CHO AA8), and one rodent and mortal (C3H 10T1/2), were investigated. The first two showed a strong correlation between radiation sensitivity and PE, even when, for the mortal cells, the effect of passage number was factored out.

Animals↗
PubMed1986

Ozone acts alone and synergistically with ionizing radiation to induce in vitro neoplastic transformation.

Ozone, a major chemical oxidant in the atmosphere, is an environmental air pollutant whose ability to act as a direct carcinogen is unclear Using in vitro transformation, a technique which permits the study of oncogenesis in the absence of host specific effects, we report for the first time that ozone (5 p.p.m. for 5 min) induces neoplastic transformation in vitro in both primary hamster embryo cells and mouse fibroblast cultures (C3H/10-1/2). Exposure of the hamster and mouse cells to ozone also results in enhanced levels of free radical-mediated lipid peroxidation products. We also report for the first time on the carcinogenic interaction between ozone and ionizing radiation. Exposure of the cells to 3 or 4 Gy of gamma-rays, 2 h prior to O3 treatment, results in markedly enhanced rates of transformation, statistically consistent with a synergistic interaction between the agents. The results demonstrate that O3 acts as a direct carcinogen and co-carcinogen on susceptible cells, therefore having important consequences for public health.

Cell Line↗
PubMed1985

Potentially lethal damage repair in cell lines of radioresistant human tumours and normal skin fibroblasts.

Radiation cell survival data were obtained in vitro for three cell lines isolated from human tumours traditionally considered to be radioresistant--two melanomas and one osteosarcoma--as well as from a diploid skin fibroblast cell line. One melanoma cell line was much more radioresistant than the other, while the osteosarcoma and fibroblast cell lines were more radiosensitive than either. For cells growing exponentially, little potentially lethal damage repair (PLDR) could be demonstrated by comparing survival data for cells in which subculture was delayed by 6 h with those sub-cultured immediately after treatment. For the malignant cells in plateau phase, which in these cells might be better termed 'slowed growth phase', since an appreciable fraction of the cells are still cycling, a small amount of PLDR was observed, but not as much as reported by other investigators in the literature. The normal fibroblasts, which achieved a truer plateau phase in terms of noncycling cells, showed a significantly larger amount of PLDR than the tumour cells.

Cell Cycle↗
PubMed1985

Dual radiation action and the initial slope of survival curves.

The concepts and tools of the Theory of Dual Radiation Action (e.g., proximity functions and gamma distributions) are outlined, and their connection to single-event cell inactivation is exemplified by an analysis and interpretation of the cross-section data obtained by Todd. It is shown that the biological effect of individual charged particles is dominated by the combined action of a few delta rays.

Animals↗
PubMed1985

On the microdosimetric definition of quality factors.

A formulation of the concept of quality factor based on the microdosimetric quantity lineal energy, y, is described. Toward this end, functions--denoted Specific Quality Functions (SQF)--are defined such that (a) they can be determined directly from observation and (b) a number of them can be used toward setting, by consensus, the values of a microdosimetrically-based quality factor. The determination of SQFs is exemplified by correlating data on the yields of dicentric aberrations in human lymphocytes with measured and calculated microdosimetric distributions. The implications of this approach to problems of radiation protection are discussed.

Alpha Particles↗
PubMed1984

The application of track calculations to radiobiology. II. Calculations of microdosimetric quantities.

In this second paper of a series, Monte Carlo-simulated proton tracks in water vapor are analyzed to yield a range of quantities that are of radiobiological interest. These include proximity functions of energy deposition, lineal energy distributions in micrometer and nanometer site sizes, and radial energy distributions. Many of these quantities cannot be measured with current experimental techniques. Some results are compared with those from analytic calculations. Also the effect on such quantities of the uncertainties in cross-sectional data used in the original Monte Carlo calculations is assessed, as is the effect of including nonionizing energy-loss events for analysis in the calculation.

Energy Transfer↗
PubMed1984

Modification of the theory of dual radiation action for attenuated fields. I. Basic formalism.

A modification of the Theory of Dual Radiation Action is described to take into account the effects of an attenuated beam of radiation across the sensitive site of the cell. It is shown that, unlike the case of uniform radiation, the coefficient of the dose-squared (intertrack) term is not constant, but varies in a manner dependent on the attenuation coefficient of the radiation and the geometry of the site.

Cell Survival↗
PubMed1984

Modification of the theory of dual radiation action for attenuated fields. II. Application to the analysis of soft X-ray results.

A formalism developed in the first paper in this series, based on the generalized Theory of Dual Radiation Action, is applied to survival data for cells exposed to soft X rays. It is shown that, in contrast to previous published analyses, this formalism--modified to account for the attenuation of dose across the sensitive matrix of the cell--is fully consistent with the experimental results. The reasons for previous disagreements are discussed.

Cell Survival↗
PubMed1984

The application of track calculations to radiobiology. III. Analysis of the molecular beam experiment results.

Survival data from the molecular beam experiment are used to obtain an estimate of the function gamma (chi), describing the probability for two energy transfers a distance chi apart to produce a lesion. A comparison is made between the functions gamma (chi) obtained using proximity functions calculated with Monte Carlo-generated tracks and with simplifying assumptions (the LET approximation). The results differ substantially, which shows that the results are very sensitive to the degree of detail used in characterizing the physics of the irradiating field.

Cell Survival↗
PubMed1984

On the stochastic treatment of fast chemical reactions.

A Monte Carlo code was developed to stimulate stochastically the fast reactions of radiolysis products in water. The results of these calculations show that treatments based on deterministic kinetic rate equations do not reproduce correctly the evolution in time of the number of species. Ad hoc initial distributions of species in spurs, of the type used in deterministic approaches, are compared with more realistic distributions obtained from Monte Carlo-generated particle tracks. The effects of using either type of distribution, stochastically or deterministically, are discussed.

Electrons↗