Radiobiology of ultrasoft X rays. V. Modification of cell inactivation by dimethyl sulfoxide.

The effects of the radioprotector dimethyl sulfoxide (DMSO) were investigated for carbon-K (0.28 keV) and aluminum-K (1.47 keV) X rays compared with 60Co gamma rays for inactivation of mouse C3H 10T1/2 cells. The protection factor for 2 M DMSO was found to be 2.8 for both of the ultrasoft X-ray energies, which is not significantly different from the protection factor of 2.6 found for gamma rays. The results indicate that the proportion of scavengeable lethal damage from gamma and X rays does not depend on the proportion of the total energy that is deposited by low-energy electrons of relatively high ionization density.

Radiobiology of ultrasoft X rays. II. Cultured C3H mouse cells (10T1/2).

In the first paper of this series (Radiat. Res. 110, 396-412 (1987], using V79 cells, we reported that the relative biological effectiveness (RBE) of ultrasoft X rays was found to increase with decreasing energy, and the oxygen enhancement ratio (OER) was found to decrease with decreasing energy. In this report, we present RBE and OER results for 10T1/2 cells that are known to grow uniformly flat and are considerably thinner than V79 cells. Thus the variation in dose across the cell nucleus is considerably reduced. The OER results agree well with our earlier V79 results. However, the RBE values for 10T1/2 cells compared to V79 cells are systematically less for all soft X rays and especially for 0.28 keV carbon-K (1.3 compared to 3.4 for V79 cells). Some plausible explanations are presented to reconcile the apparent discrepancy between V79 and 10T1/2 results.

Radiobiology of ultrasoft X rays. III. Normal human fibroblasts and the significance of terminal track structure in cell inactivation.

Ultrasoft characteristic X rays from carbon (0.28 keV) are severely attenuated as they pass through biological material, causing a nonuniform distribution of dose to cell nuclei. Complications of studying ultrasoft X rays can be minimized in this context by using cells with very thin cytoplasm and nuclei (e.g., less than the attenuation length of the X rays), and which exhibit a more nearly exponential dose response to cell killing, such as normal human fibroblasts compared with V79 cells. Using this cell system, we report the relative biological effectiveness (RBE) of A1-K and C-K X rays to be near unity. Previous studies of cell inactivation by characteristic carbon X rays gave RBEs of 3 to 4, supporting the idea that localized energy depositions from secondary electrons and primary track ends represent the principal mode of biological action for other low-LET radiations. In part, the reported high RBEs result from the use of mean dose to describe energy deposited within the cell nuclei by these poorly penetrating radiations. Implicit in the use of mean dose is that cellular damage varies linearly with dose within a critical target(s), an assumption that is of questionable validity for cells that exhibit pronounced curvilinear dose responses. The simplest interpretation of the present findings is that most energy depositions caused by track-end effects are not necessarily more damaging than the sparsely ionizing component.

Radiobiology of ultrasoft X rays. IV. Flat and round-shaped hamster cells (CHO-10B, HS-23).

The results reported earlier in this series indicated that the relative biological effectiveness (RBE) of ultrasoft X rays decreases with decreasing cell thickness, approaching unity for the thinnest cells used, plateau-phase human skin fibroblasts (HSF). The possible dependence of RBE on the configuration of the cell nucleus is investigated further in this paper using two CHO cell lines that attach well and have similar intrinsic radiosensitivities to 60Co gamma rays. One of the lines forms monolayers similar to V79 cells, while the other remains more spherical during growth. We find an increasing RBE with decreasing X-ray energy for both of these cell lines, consistent with our results using V79 cells. Also consistent with our results obtained with 10T1/2 and HSF cells, we find an increasing RBE with increasing cell thickness. The possible dependence of RBE on radiosensitivity and the use of the concept of mean dose for ultrasoft X rays is discussed.

Radiobiology of ultrasoft X rays. I. Cultured hamster cells (V79).

Ultrasoft X rays (approximately less than keV) provide a useful probe for the study of the physical parameters associated with the induction of biological lesions because the spatial scale of their energy depositions is of nanometer dimensions, comparable to that of critical structures within the cell. We report on cell-killing experiments using cultured hamster cells (V79) exposed to carbon K (0.28 keV), aluminum K (1.5 keV), copper K (8.0 keV), and 250 kVp X rays, under oxic and hypoxic conditions, and as a function of cell-cycle phase. Our principal results are: RBE increases with decreasing X-ray energy; OER decreases with decreasing X-ray energy; and cell-cycle response is similar for all X-ray energies. Our RBE results confirm earlier observations using ultrasoft X rays on mammalian cells. The shapes of fitted curves through the data for each energy are statistically indistinguishable from one another, implying that the enhanced effectiveness is purely dose modifying. The results reported herein generally support the view that single-track effects of radiation are predominantly due to very local energy depositions on the nanometer scale, which are principally responsible for observed radiobiological effects.

Measurement of the G-value for 1.5 keV X-rays.

Although there are several theoretical predictions of the dependence of the G-value on X-ray energy, measurements have not been made below approximately equal to 7 keV. Using a ferrous sulfate solution modified by the addition of benzoic acid, we have measured the relative G-values for Alk characteristic X-rays (1.5 keV), 238Pu alpha-particles (3.7 MeV), 60Co (1.17 MeV) and 137Cs (0.66 MeV) gamma-rays. This modified ferrous sulfate solution gave a 4-fold increase in sensitivity relative to the conventional solution, making measurements with the Alk X-rays feasible. The relative ferrous-to-ferric conversions as a function of dose were similar for the two gamma-ray energies, yielding G-values of 1.62 and 1.59 mumol J-1 for the 60Co and 137Cs radiations, respectively. The alpha-particle G-value was 0.52 mumol J-1, or 31 per cent of that for the 60Co gamma-rays, in good agreement with previous measurements. The Alk X-rays had a G-value of 0.92 mumol J-1 or 57 per cent of that of the 60Co radiation. This G-value for the 1.5 keV X-rays is within 20 per cent of the values predicted by current theories, and theoretical values are within the error range of our measurement. The consistency between the experimental value reported here and theoretical G-values for ultrasoft X-rays should be valuable for models of radiation action on biological systems.

Dose outside the treatment volume for irradiation with negative pions.

Irradiation of humans with negative pions requires a knowledge of the absorbed dose and radiation quality outside the primary pion beam. In conjunction with early clinical trials at LAMPF, experimental data have been obtained with microdosimetric techniques and multiwire proportional counters. Theoretical calculations have been made for the neutron contribution to the dose and are consistent with these data. Measurements were made with in 40 cm x 51 cm x 76 cm water phantom for a negative pion beam of initial momentum of 170 MeV/c, deltap = +/- 3MeV/c. The absorbed dose outside the treatment volume is the result of: (1) neutrons and photons from the pion interactions,(2) treatment room background and (3) peripheral muons, electrons and pions in the primary beam. The first two components are nearly isotropic and are congruent to 0.02% of the peak dose at a distance of 24 cm from the treatment volume; the third component is anisotropic and varies from 0.01 to 0.1% of the peak dose. Collimation of the bean increases the dose outside the treatment volume typically by 50%.

Analyzing bioassay data using Bayesian methods--a primer.

The classical statistics approach used in health physics for the interpretation of measurements is deficient in that it does not take into account "needle in a haystack" effects, that is, correct identification of events that are rare in a population. This is often the case in health physics measurements, and the false positive fraction (the fraction of results measuring positive that are actually zero) is often very large using the prescriptions of classical statistics. Bayesian statistics provides a methodology to minimize the number of incorrect decisions (wrong calls): false positives and false negatives. We present the basic method and a heuristic discussion. Examples are given using numerically generated and real bioassay data for tritium. Various analytical models are used to fit the prior probability distribution in order to test the sensitivity to choice of model. Parametric studies show that for typical situations involving rare events the normalized Bayesian decision level k(alpha) = Lc/sigma0, where sigma0 is the measurement uncertainty for zero true amount, is in the range of 3 to 5 depending on the true positive rate. Four times sigma0 rather than approximately two times sigma0, as in classical statistics, would seem a better choice for the decision level in these situations.

Bayesian prior probability distributions for internal dosimetry.

The problem of choosing a prior distribution for the Bayesian interpretation of measurements (specifically internal dosimetry measurements) is considered using a theoretical analysis and by examining historical tritium and plutonium urine bioassay data from Los Alamos. Two models for the prior probability distribution are proposed: (1) the log-normal distribution, when there is some additional information to determine the scale of the true result, and (2) the 'alpha' distribution (a simplified variant of the gamma distribution) when there is not. These models have been incorporated into version 3 of the Bayesian internal dosimetry code in use at Los Alamos (downloadable from our web site). Plutonium internal dosimetry at Los Alamos is now being done using prior probability distribution parameters determined self-consistently from population averages of Los Alamos data.

Internal dosimetry for inhalation of hafnium tritide aerosols.

Metal tritides with low dissolution rates may have residence times in the lungs which are considerably longer than the biological half-time normally associated with tritium in body water, resulting in long-term irradiation of the lungs by low energy beta particles and bremsstrahlung X rays. Samples of hafnium tritide were placed in a lung simulant fluid to determine approximate lung dissolution rates. Hafnium hydride samples were analysed for particle size distribution with a scanning electron microscope. Lung simulant data indicated a biological dissolution half-time for hafnium tritide on the order of 10(5) d. Hafnium hydride particle sizes ranged between 2 and 10 microns, corresponding to activity median aerodynamic diameters of 5 to 25 microns. Review of in vitro dissolution data, development of a biokinetic model, and determination of secondary limits for 1 micron AMAD particles are presented and discussed.