Carcinogenic risk coefficients at environmental levels of radon exposures: a microdosimetric approach.

We report a microdosimetric-based evaluation of the effects of domestic exposure to radon. The risk coefficients obtained here are based on the microdosimetry of radon progeny alpha particles, on a function q(y) for in vivo radiogenic neoplasia, and on scaling A-bomb results (epidemiology + microdosimetry) to radon exposure. We do not use miner data, nor do we invoke such notions as quality factors, dose equivalent or equivalent dose. With basal cells as targets our estimated risk coefficients are in good agreement with the miner data, and thus a quality factor of about 20 (as suggested by ICRP 60) is not unreasonable. However, if we take as targets the secretory cells our risk coefficients are twice as large as those reported by BEIR-IV. The main uncertainty in these estimates remains the dosimetric model.

An inductive assessment of radiation risks in space.

Procedures for the assessment of risks or vulnerabilities from radiation in space are evaluated in terms of model-independent inductive approaches. The reliability of risks calculated for space applications on the basis of accelerator-based physical and biological data is examined from a microdosimetric perspective. Probability distributions for energy deposition in biologically significant sites extend over several decades in lineal energy even for monoenergetic high-energy particles of relatively high atomic number. Because the response depends on a large number of variables and because of the difficulty of incorporating all such factors into calculations, a precise correlation between a physical descriptor of the field and observed effects in space is not feasible. For the same reasons, it is equally difficult to estimate the accuracies of such risk assessments. We use recently published microdosimetric spectra for HZE particles and biological weighting functions, including those derived from biological measurements with maximum entropy techniques, to illustrate some problems associated with the evaluations of risks from radiation fields in space.

Computational biology opportunity and challenges for the future.

Recent developments in high performance computers and computing methods have opened new avenues for tackling serious, important and challenging problems in biology and medicine. Only a few years back these problems were considered too complex and difficult, if not impossible to solve. An understanding of cross-disciplinary knowledge will be a prerequisite for applications of this enormous computing capability to enhance our understanding of governing principals in biology and medicine. We will show some specific research areas where computational biology can be applied effectively and then provide some ideas on future applications.

Radial distribution of dose.

The radial distribution of dose about the path of a heavy ion, principally from delta rays, is one of the central contributions of atomic physics to the systematization of high LET radiation effects in condensed matter, whether the detection arises in chemical, physical, or biological systems. In addition to the radial distribution of dose, we require knowledge of the response of the system to X-rays or gamma-rays or to beams of energetic electrons such that the electron slowing-down spectra from these radiations can approximate the slowing-down spectra from delta rays even at different radial distances from the ion's path. A combination of these data enables us to calculate the action cross sections ion bombardments in all detectors for which this information is available. These cross sections are indispensable for the evaluation of effects caused by high LET radiations. In this paper we focus attention principally on the calculation and measurement of the radial distribution of dose and on their limitations.

Age related toxic effects of endosulfan on certain enzymes of rat erythrocytes.

The effect of oral administration of endosulfan (12.5 mg/kg body weight), daily for 4 days was investigated on erythrocytes of female rats of 4 different age groups i.e. 15, 30, 70 and 365 days old. Erythrocyte membrane Na+, K(+)-ATPase and Mg2(+)-ATPase activities were significantly inhibited in all the age groups of rats. However, percent inhibition was maximum in the youngest animals. A significant decrease in the activity of erythrocyte glutathione reductase was observed in 30 and 70 days old rats whereas a significant increase in the activity of glucose-6-phosphate dehydrogenase (G-6-PD) was observed in these groups. The increase in G-6-PD activity may be a physiological response to compensate for decrease in the reduced glutathione level which results from decrease in the activity of glutathione reductase.

Biochemical studies on endosulfan toxicity in different age groups of rats.

The effect of oral administration of endosulfan (12.5 mg/kg body weight), daily, for 4 days was investigated in female rats of 4 different age groups, i.e., 15, 30, 70, and 365 days old. Maximum hyperglycemia, maximum depletion of liver glycogen and maximum inhibition of brain acetylcholine esterase activity were observed in 365-day-old (adult) animals whereas these changes were found to be negligible in 15-day-old animals. A decrease in the activity of liver aldolase was observed in rats of all age groups but maximum decrease was observed in adult rats. In contrast to these changes, erythrocyte (Na+, K+)-ATPase was maximally inhibited in 15-day-old rats. These studies indicated that the toxic effects of endosulfan are age-dependent.

An alternative to absorbed dose, quality, and RBE at low exposures.

The microdosimetric distribution of event sizes, especially for small exposures and high-LET radiation, represents both a fractional involvement of the exposed cell population and variable amounts of energy transferred to the "hit" cells. To determine the fraction of cells that will respond quantally (be transformed) after receiving a hit of a given size, a hit size effectiveness function (HSEF) which appears to have a threshold has been derived from experimental data for pink mutations in Tradescantia. The value of the HSEF at each event size, multiplied by the fractional number of cells hit at that event size, and summed over all event sizes, yields a single value representing the fractional number of quantally responding cells and thus the population impairment for a given exposure. The HSEF can be obtained by unfolding (deconvoluting) several sets of biological and microdosimetric data obtained with radiation of overlapping event size distributions.

Stopping power and radial dose distribution for 42 MeV bromine ions.

Linear energy transfer restricted in radius (LETr) and total linear energy transfer (LET infinity) were determined for 42 MeV bromine ions in tissue-equivalent gas. A variable pressure cylindrical ionisation chamber was used. Dose as a function of distance from the ion's path was also determined using a mesh wall ionisation chamber placed inside the cylindrical chamber. The range of distances studied was from 5 to 710 A in simulated tissue of unit density. Experimentally obtained values of radial dose were compared with calculations made using Paretzke's program. Stopping power for these ions in tissue-equivalent gas was extrapolated from proton stopping power in constituent gases. In this calculation the effective charge of the ions was obtained from the formula given by Dimitriev and Nikolaev. This calculated value was 6.3 x 10(4) MeV g-1 cm2. The experimentally determined value was 7.3 x 10(4) MeV g-1 cm2. The discrepancy between calculated and experimental values may be due to uncertainty in the determination of the effective charge of the incident ions. Uncertainty on the experimental value of LET infinity was estimated to be +/- 5% (one standard deviation).

Relative determination of W-values for alpha particles in tissue-equivalent and other gases.

W (the average energy to form an ion pair) for 5.4 MeV 241Am alpha particles in a Rossi-type tissue-equivalent (TE) gas, argon and methane was determined to an accuracy better than 0.2% using a new automated data handling system. A vibrating reed electrometer and current digitiser were used to measure the current produced by completely stopping the alpha particles in a large cylindrical ionisation chamber. A multichannel analyser, operating in a slow multiscaler mode, was used to store pulses from the current digitiser. The dwell time, of the order of 60 min per channel, was selected with an external timer gate. Current measurements were made at reduced pressures (200 Torr) to reduce ion recombination. The average current, over many repeated measurements, was compared to the current produced in nitrogen and its previously published W-value of 36.39+/-0.04 eV per ion pair. The resulting W-values were, in eV per ion pair, 26.29+/-0.05 for argon, 29.08+/-0.03 for methane and 30.72+/-0.04 for TE gas, which had an analysed composition of 64.6% methane, 32.4% CO2 and 2.7% nitrogen. Although the methane and argon values agree within 0.1% with previously published values, the value for TE is 1.2% lower than the single previously reported value.

Energy dependence of W for alpha particles in N2, CO2, CH4, Ar, H2 and Rossi-type tissue-equivalent gases.

Average energy required to form an ion pair (W) was determined in N2, CO2, CH4, Ar, H2 and Rossi-type tissue-equivalent gas. Alpha particles from a 241Am source were used. W was determined at alpha energies of 5.37, 3.12, 1.08 and 0.46 MeV. The ratio of total ionisation produced (for fixed alpha particle energy) in experimental gas to that produced in argon was measured. This ratio was then multiplied by the previously determined W value for argon gas (26.29 eV per ion pair) to yield W for various experimental gases. Energy of the 241Am alpha particles was degraded by using air as an absorbing material. Empirical relations W = alpha + betaE-1/2 and W = alpha1 + beta1E-1 were fitted to the experimental data. Both functions fit reasonably well in the range 0.4--5.37 MeV. Below about 0.4 MeV the first function provides a better fit to the data of Boring et al. (1965).

Experimental determination of W for oxygen ions in nitrogen.

'Differential' and integral measurements were made of the W value (average energy required to form an ion pair) for oxygen ions in nitrogen gas. A variable pressure cylindrical ionization chamber with a differential pumping section was employed. The average energy deposited per particle in the chamber was determined by integrating the energy spectrum measured with a heavy ion solid state detector. In the integral measurement of W, the particle was completely stopped in the chamber and the total ionization produced in the chamber was measured. The integral W value for 34-5 MeV oxygen ions was found to be 38-6 +/- 0-54 eV per ion pair. For 'differential' measurements, the pressure in the chamber was raised to 0-003, 1, 5, 15 and 20 Torr; and measurements of ionization currents and average energy deposited per particle were made at each pressure. From differences between these measurements 'differential' W was found. The average value of fifteen 'differential' W values was found to be 38-6 +/- 1-16 eV per ion pair.