Hydroxycobalamin catalyzes the oxidation of diethyldithiocarbamate and increases its cytotoxicity independently of copper ions

It is known that some metals (Cu, Zn, Cd, Au) markedly increase the toxic effect of thiocarbamates. It was shown in the present study that hydroxycobalamin (a form of vitamin B12, HOCbl), which incorporates cobalt, significantly enhances the cytotoxicity of diethyldithiocarbamate (DDC), decreasing its IC50 value in tumor cells three to five times. The addition of HOCbl to aqueous DDC solutions accelerated the reduction of oxygen. No hydrogen peroxide accumulation was observed in DDC + HOCbl solutions; however, catalase slowed down the oxygen reduction rate. Catalase as well as the antioxidants N-acetylcysteine (NAC) and glutathione (GSH) partially inhibited the cytotoxic effect of DDC + HOCbl, whereas ascorbate, pyruvate, and tiron, a scavenger of superoxide anion, had no cytoprotective effect. The administration of HOCbl into DDC solutions (> 1 mM) resulted in the formation of a crystalline precipitate, which was inhibited in the presence of GSH. The data of UV and NMR spectroscopy and HPLC and Mass Spectrometry (LC/MS) indicated that the main products of the reaction of DDC with HOCbl are disulfiram (DSF) and its oxidized forms, sulfones and sulfoxides. The increase in the cytotoxicity of DDC combined with HOCbl occurred both in the presence of Cu2+ in culture medium and in nominally Cu-free solutions, as well as in growth medium containing the copper chelator bathocuproine disulfonate (BCS). The results indicate that HOCbl accelerates the oxidation of DDC with the formation of DSF and its oxidized forms. Presumably, the main cause of the synergistic increase in the toxic effect of DDC + HOCbl is the formation of sulfones and sulfoxides of DSF. Keywords: Diethyldithiocarbamate, Disulfiram, Hydroxycobalamin, Vitamin B12, Oxidative stress, Cytotoxicit

Convolution of TLD and SSNTD measurements during the BRADOS-1 experiment onboard ISS (2001)

The Russian BRADOS experiment onboard the International Space Station (ISS) was aimed at developing methods in radiation dosimetry and radiobiology to improve the reliability of risk estimates for the radiation environment in low-Earth orbit. Experimental data from thermoluminescence detectors (TLDs) and solid state nuclear track detectors (SSNTDs) gathered during the BRADOS-1 (24 February–31 October 2001) mission are reviewed and convolved to obtain absorbed dose and dose equivalent from primary and secondary cosmic-ray particles. Absorbed dose rates in the ISS Russian Segment (Zvezda) ranged from 208 ± 14 to 275 ± 14 µGy d-1. Dose equivalent rates were determined to range from 438 ± 29 to 536 ± 32 µSv d-1, indicating a quality factor between 1.95 ± 0.15 and 2.11 ± 0.20. The contribution of densely ionizing particles (LET≥10 keV µm-1) to dose equivalent made up between 54% and 64%

TL dose measurements on board the Russian segment of the ISS by the “Pille” system during Expedition-8, -9 and -10

The “Pille-MKS” thermoluminescent (TL) dosimeter system developed by the KFKI Atomic Energy Research Institute (KFKI AEKI) and BL-Electronics, consisting of 10 CaSO4:Dy bulb dosimeters and a compact reader, has been continuously operating on board the International Space Station (ISS) since October 2003. The dosimeter system is utilized for routine and extravehicular activity (EVA) individual dosimetry of astronauts/cosmonauts as part of the service system as well as for on board experiments, and is operated by the Institute for Biomedical Problems (IBMP). The system is unique in that it regularly provides accurate dose data right on board the space station, a feature that became increasingly important during the suspension of the Space Shuttle flights. Seven dosimeters are located at different places of the Russian segment of the ISS and are read out once a month. Two of these dosimeters are dedicated to EVAs and one is kept in the reader and will be read out automatically every 90 min. During coronal mass ejections impacting Earth some of the dosimeters serve for individual monitoring of the astronauts with readouts once or twice every day. In this paper we report the results of dosimetric measurements made on board the ISS during Expedition-8, -9 and -10 using the “Pille” portable thermoluminescent detector (TLD) system and we compare them with our previous measurements on different space stations