DNA Topoisomerase IB as a Potential Ionizing Radiation Exposure and Dose Biomarker.

In radiation exposure scenarios where physical dosimetry is absent or inefficient, dose estimation must rely on biological markers. A reliable biomarker is of utmost importance in correlating biological system changes with radiation exposure. Human DNA topoisomerase ІB (topo І) is a ubiquitous nuclear enzyme, which is involved in essential cellular processes, including transcription, DNA replication and DNA repair, and is the target of anti-cancer drugs. It has been shown that the cellular activity of this enzyme is significantly sensitive to various DNA lesions, including radiation-induced DNA damages. Therefore, we investigated the potential of topo I as a biomarker of radiation exposure and dose. We examined the effect of exposure of different human cells to beta, X-ray and gamma radiation on the cellular catalytic activity of topo I. The results demonstrate a significant reduction in the DNA relaxation activity of topo I after irradiation and the level of the reduction was correlated with radiation dose. In normal human peripheral blood lymphocytes, exposure for 3 h to an integral dose of 0.065 mGy from tritium reduced the enzyme activity to less than 25%. In MG-63 osteoblast-like cells and in human pulmonary fibroblast (HPF) cells exposed to gamma radiation from a 60Co source (up to 2 Gy) or to X rays (up to 2.8 Gy), a significant decrease in topo I catalytic activity was also observed. We observed that the enzyme-protein level was not altered but was partially posttranslational modified by ADP-ribosylation of the enzyme protein that is known to reduce topo I activity. The results of this study suggest that the decrease in the cellular topo I catalytic activity after low-dose exposure to different radiation types may be considered as a novel biomarker of ionizing radiation exposure and dose. For this purpose, a suitable ELISA-based method for large-scale analysis of radiation-induced topo I modification is under development.

On the photon self-absorption correction for thin-target-yields vs. thick-target-yields in radionuclide production.

In the experimental determination of activity of low gamma energy emitters by HPGe spectrometry, after cyclotron irradiation of thick targets of high Z elements, it is mandatory to introduce a correction for gamma-ray self-absorption in the target. The amount of this correction is substantial in order to provide a statistically acceptable agreement with the thick-target-yield data obtained by integration of the experimental thin-target-yield data that are very slightly affected by self-absorption instead.

Improved determination of the position and activity of a radioactive point source inside a bulky medium using several detectors. The special case of a lung counter--a general view.

A method is described to locate a radioactive point source in a lung using a commercial array of lung detectors. The method takes advantage of the fact that modern commercial systems consist of several Ge detectors, each connected to a multi-channel analyzer, and the information from each detector can be analyzed separately. The system is calibrated with point sources placed in various locations in the lungs of a phantom. A vector method is presented for determining which of the calibration locations in the phantom is closest to the location of the unknown point source. It has been shown that the accuracy of the method increases with increasing number of the vector dimensions. A higher dimensionality can be achieved by analyzing counts of several gamma lines or by using more detectors.

On the "artificial" nature of Tc and the "carrier-free" nature of 99mTc from 99Mo/99mTc generators.

Two widespread misconceptions regarding Tc are dealt with. First, it is shown that although primordial Tc has decayed completely, Tc is still present in nature due to natural processes, in addition to substantial man-made quantities. Thus, Tc cannot be considered as a purely artificial element. Second, it is shown that (99m)Tc from (99)Mo/(99m)Tc generators is certainly not carrier-free (CF) and that, "no-carrier-added" (NCA) is a more appropriate designation. As a quantitative measure of the amount of long-lived (99g)Tc carrier present in (99m)Tc preparations from generators, the Isotope Dilution Factor (IDF) is used and calculated for some practical situations.

On the normalization of a mass spectrum for comparison of two spectra.

It is indicated that for comparison of two mass-spectra the normalization of each ion current should be done such that each spectrum will form a unit vector, i.e., SigmaXi2 = 1, where Xi are the various components of the mass spectrum.

Location-independent determination of the activity of a point source in absorbing media.

The unknown distribution of a radioactive material in a bulky volume will induce considerable inaccuracies in the determination of its activity due to the unknown geometry and absorption factors. The methods of using two detectors and of employing the full-energy peak to total ratio were investigated to evaluate parameters, which can be used to improve the accuracy of activity determination.

The validity of the virtual point detector concept for absorbing media.

The concept of representing the detector volume by a virtual point detector in order to facilitate efficiency evaluations was proposed in the past for non-absorbing media. The validity of the model was expanded also to absorbing media present between the detector and a point source in front of it. Empirical values were determined based on experiments with aluminum, copper, iron and lead.

On the comparison of different tests for identification of a compound from its mass spectrum.

It is shown that identification tests of different dimensions or dimensionless should not be evaluated (for their efficiency to identify molecules from their mass spectrum) by comparing the tests for a molecule itself (repeated measurements) with other molecules. This kind of tests must have similar dimensions (units). Another possibility is the comparison of tests on the basis of success of correct prediction for "unknown" molecules from a library of standards.