The intercomparison of cosmic rays with heavy ion beams at NIRS (ICCHIBAN) project.

The ICCHIBAN-2 experiment, the first dedicated to the ground-based intercomparison of passive space dosemeters, was carried out between 23 May and 28 May 2002 at the National Institute of Radiological Sciences in Chiba, Japan. The primary objective of the ICCHIBAN-2 experiment was to intercompare the response of passive dosemeters used in space crew dosimetry to monoenergetic heavy ions of charge and energy spanning a significant portion of the galactic cosmic ray (GCR) spectrum. During the ICCHIBAN-2 experiment, dosemeters from 12 different laboratories in 9 countries were irradiated under identical conditions to heavy ion beams of 150 MeV n(-1) (4)He, 400 MeV n(-1) (12)C, 490 MeV n(-1) (28)Si and 500 MeV n(-1) (56)Fe at the NIRS Heavy Ion Medical Accelerator.

Reduction in life span of normal human fibroblasts exposed to very low-dose-rate charged particles.

We studied the effect of chronic low-dose irradiation with heavy ions on the life span of normal human fibroblasts in vitro. Cells were cultured in a CO2 incubator that was placed in the irradiation room for biological studies of heavy ions in the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS) and were exposed to scattered radiations produced by heavy-ion beams for the life span of the cell population. The absorbed dose, which was measured using a thermoluminescence dosimeter (TLD) and a silicon semiconductor detector, was 1.4 mGy per day when the HIMAC was operated for biological experiments. The total number of population doublings of the exposed cells as reduced to 79-93% of that of nonexposed control cells. However, the life span of cells exposed to low-dose 137Cs gamma rays (approximately 1 mGy/day) in the CO2 incubator in the gamma-irradiation room in NIRS was prolonged to 104-106% of that of nonexposed control cells. Thus there is evidence that exposure to chronic low-dose heavy-ion radiation reduces the life span of cells.

Differential absorbed dose distributions in lineal energy for neutrons and gamma rays at the mono-energetic neutron calibration facility.

Absorbed dose distributions in lineal energy for neutrons and gamma rays of mono-energetic neutron sources from 140 keV to 15 MeV were measured in the Fast Neutron Laboratory at Tohoku University. By using both a tissue-equivalent plastic walled counter and a graphite-walled low-pressure proportional counter, absorbed dose distributions in lineal energy for neutrons were obtained separately from those for gamma rays. This method needs no knowledge of energy spectra and dose distributions for gamma rays. The gamma-ray contribution in this neutron calibration field >1 MeV neutron was <3%, while for <550 keV it was >40%. The measured neutron absolute absorbed doses per unit neutron fluence agreed with the LA150 evaluated kerma factors. By using this method, absorbed dose distributions in lineal energy for neutrons and gamma rays in an unknown neutron field can be obtained separately.

Experimental microdosimetric distributions of protons, from 19 to 65 MeV, using an A150-walled Low Pressure Proportional Counter.

Microdosimetric distributions of protons, from 19 to 65 MeV, were measured using an A150-walled Low Pressure Proportional Counter at the cyclotron facility in the National Institute of Radiological Sciences. The measured distributions were found to be very different from the spectra assumed by the Continuous Slowing Down Approximation. The measurements consisted of determining the energy deposition by direct incident protons, by secondary electrons produced in the wall of the detector and by scattered protons at the wall. The secondary electron and the scattered proton distributions were studied using analytical functions and the MCNPX Monte Carlo code, respectively.

Glutathione S-transferase-pi gene expression and platinum drug exposure in human lung cancer.

We examined the association between the gene expression levels of glutathione S-transferase-pi (GST-pi) and platinum drug exposure in human lung cancer. First we monitored GST-pi gene expression levels in two lung cancer cell lines and in peripheral mononuclear cells of ten previously untreated lung cancer patients after platinum drug exposure. Next we examined GST-pi gene expression levels in 40 lung cancer autopsy specimens. The GST-pi gene expression levels were assessed by the quantitative reverse transcription-polymerase chain reaction or Northern blot analysis. The GST-pi gene expression was not induced by platinum drugs either in vitro and in vivo within 24 h of exposure. In contrast, GST-pi gene expression levels in lung cancer tissues of patients who had been exposed to platinum drugs at least 1 month before death were significantly higher than that in those of patients who had not been exposed. These results suggest that GST-pi gene expression is associated with chronic exposure to platinum drugs in lung cancer and/or the stress response to xenobiotics.

Effective dose equivalent on the ninth Shuttle--Mir mission (STS-91).

Organ and tissue doses and effective dose equivalent were measured using a life-size human phantom on the ninth Shuttle-Mir Mission (STS-91, June 1998), a 9.8-day spaceflight at low-Earth orbit (about 400 km in altitude and 51.65 degrees in inclination). The doses were measured at 59 positions using a combination of thermoluminescent dosimeters of Mg(2)SiO(4):Tb (TDMS) and plastic nuclear track detectors (PNTD). In correcting the change in efficiency of the TDMS, it was assumed that reduction of efficiency is attributed predominantly to HZE particles with energy greater than 100 MeV nucleon(-1). A conservative calibration curve was chosen for determining LET from the PNTD track-formation sensitivities. The organ and tissue absorbed doses during the mission ranged from 1.7 to 2.7 mGy and varied by a factor of 1.6. The dose equivalent ranged from 3.4 to 5.2 mSv and varied by a factor of 1.5 on the basis of the dependence of Q on LET in the 1990 recommendations of the ICRP. The effective quality factor (Q(e)) varied from 1.7 to 2.4. The dose equivalents for several radiation-sensitive organs, such as the stomach, lung, gonad and breast, were not significantly different from the skin dose equivalent (H(skin)). The effective dose equivalent was evaluated as 4.1 mSv, which was about 90% of the H(skin).

Induction of cytochrome P450 3A4 by docetaxel in peripheral mononuclear cells and its expression in lung cancer.

Several recent studies have demonstrated that the cytochrome p450 (CYP) family plays an important role in the metabolism of taxanes. However, the role of CYP gene expression in tumors and peripheral mononuclear cells (PMN) is unknown. We therefore investigated the levels of CYP3A4 and CYP2C gene expression using reverse transcription polymerase chain reaction (RT-PCR) in PMN from 16 previously untreated lung cancer patients to determine whether the expression of the two genes is induced by docetaxel (TXT). Neither the CYP3A4 nor the CYP2C gene was induced after administration of carboplatin (CBDCA) alone. Expression of the CYP3A4 gene was induced by the administration of TXT alone or TXT and CBDCA, but expression of the CYP2C gene was unaffected. We also measured the expression of both genes using RT-PCR in 20 autopsy samples (ten non-small-cell lung cancers and their corresponding normal lung tissues) obtained from patients who had not received any chemotherapy during life. The level of CYP2C gene expression in samples of lung cancer was significantly higher than in normal lung tissue, but the level of CYP3A4 gene expression was not. These results suggest that the CYP3A4 gene is induced by TXT, and that it plays an important role in intracellular TXT metabolism.

Expression of lung-resistance protein gene is not associated with platinum drug exposure in lung cancer.

BACKGROUND: Platinum drug resistance is an important problem in lung cancer chemotherapy. In this study, we examined lung-resistance protein (LRP) gene expression in vivo and in vitro in relation to platinum drug exposure. MATERIALS AND METHODS: The expression levels of the LRP gene were assessed by the reverse transcription polymerase chain reaction, in 80 autopsy samples (40 lung tumors and 40 corresponding normal lung tissues), two lung cancer cell lines and in peripheral mononuclear cells collected from 8 lung cancer patients before and after platinum drug administration. RESULTS: The LRP gene expression levels of autopsy specimens exposed antemortem to platinum drugs were not significantly different to those of specimens without platinum drug exposure, for both lung tumors and normal lung tissues. Our results also demonstrate that LRP gene expression was not induced by platinum drugs either in vitro or in vivo. CONCLUSIONS: The present results indicate that LRP gene expression is not associated with platinum drug exposure in lung cancer.

Carboplatin AUC and gamma-glutamylcysteine synthetase gene expression in peripheral mononuclear cells of lung cancer patients.

BACKGROUND: To investigate the association between glutathione-related enzymes and carboplatin (CBDCA) dose, we examined gene expression levels for both subunits of gamma-glutamylcysteine synthetase (heavy; gamma-GCSh, light; gamma-GCS1) in peripheral mononuclear cells (PMN) of lung cancer patients before and after CBDCA administration. MATERIALS AND METHODS: PMN and plasma samples were obtained from 10 advanced non-small lung cancer patients before and after CBDCA administration. We analyzed the gene expression levels by reverse transcription-polymerase chain reaction. RESULTS: Gamma-GCSh expression levels in PMN increased within 24 hours after CBDCA administration, whereas gamma-GCS1 expression levels did not. However, the actual area under the concentration curve (AUC) of CBDCA did not correlate with gamma-GCSh expression at 24 hours or the increased ratio of gamma-GCSh expression in PMN. CONCLUSION: Expression of gamma-GCSh is induced by CBDCA, however, CBDCA AUC is not a determinant for the increased expression levels of gamma-GCSh in PMN.

Cosmic radiation protection dosimetry using an Electronic personal Dosemeter (Siemens EPD) on selected international flights.

The effectiveness of an Electronic Personal Dosemeter (Siemens EPD) for cosmic-radiation dosimetry at aviation altitudes was examined on eight international flights between March and September, 1998. The EPD values (Hepd) of the dose equivalent from penetrating radiation, Hp(10), were assumed to be almost the same as the electron absorbed doses during those flights. Based on the compositions of cosmic radiation in the atmosphere and the 1977 ICRP recommendation, an empirical equation to conservatively estimate the personal dose equivalent (Hp77) at a depth of 5 cm was derived as Hp77 = 3.1 x Hepd. The personal dose equivalent (Hp90) based on the 1990 ICRP recommendation was given by Hp90 = 4.6 x Hepd; the conservative feature of Hp90 was confirmed in a comparison with the calculated effective doses by means of the CARI-6 code. It is thus expected that the EPD will be effectively used for radiation protection dosimetry on selected international flights.

Syndrome of inappropriate secretion of ADH (SIADH) following cisplatin administration in a pulmonary adenocarcinoma patient with a malignant pleural effusion.

We report a patient with pulmonary adenocarcinoma complicated by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following systemic chemotherapy with cisplatin (CDDP) and vindesine (VDS). A 66-year-old woman was diagnosed as having pulmonary adenocarcinoma with malignant pleural effusion following investigations for cough and dyspnea. After drainage of the effusion she received combination chemotherapy with CDDP and VDS. She developed SIADH 48 hours following chemotherapy. Interestingly, the use of carboplatin (CBDCA) and VDS in the subsequent treatment course was well tolerated indicating that the SIADH was most likely to have been induced by administration of CDDP.

Solid-state integrating detectors as an indicator of biological doses from HZE particles.

For interpretation of results obtained in future biological experiments in the International Space Station (ISS), biologically equivalent doses have to be determined using small-scale detectors without disturbing the surrounding radiation field. The detectors should be lightweight, stable, safe, and simple in handling. Solid-state integrating detectors (SSID) can satisfy these requirements. This paper demonstrates that combination of SSID such as thermoluminescence dosimeters and radiophotoluminescence glasses can be practically used for the evaluation of biologically equivalent doses. Statistical errors (type-A uncertainty) of this method will be satisfactorily small relative to those generally observed in biological responses. Permissible levels of systematic errors (type-B uncertainty) depend on dosimetry purposes (most-probable or conventional) and variability of biological responses.

Probability of cell hits in selected organs and tissues by high-LET particles at the ISS orbit.

The fluence of high-LET particles (HLP) with LET infinity H2O greater than 15 keV micrometers-1 in selected organs and tissues were measured with plastic nuclear track detectors using a life-size human phantom on the 9th Shuttle-Mir Mission (STS-91). The planar-track fluence of HLP during the 9.8-day mission ranged from 1.9 x 10(3) n cm-2 (bladder) to 5.1 x 10(3) n cm-2 (brain) by a factor of 2.7. Based on these data, a probability of HLP hits to a matured cell of each organ or tissue was roughly estimated for a 90-day ISS mission. In the calculation, all cells were assumed to be spheres with a geometric cross-sectional area of 500 micrometers2 and the cell-hit frequency from isotropic space radiation can be described by the Poisson-distribution function. As results, the probability of one or more than 1 hit to a single cell by HLP for 90 days ranged from 17% to 38%; that of two or more than 2 hits was estimated to be 1.3-8.2%.

Calibration results obtained with Liulin-4 type dosimeters.

The Mobile Radiation Exposure Control System's (Liulin-4 type) main purpose is to monitor simultaneously the doses and fluxes at 4 independent places. It can also be used for personnel dosimetry. The system consists of 4 battery-operated 256-channel dosimeters-spectrometers. We describe results obtained during the calibrations of the spectrometers at the Cyclotron facilities of the University of Louvain, Belgium and of the National Institute of Radiological Sciences-STA, Chiba, Japan with protons of energies up to 70 MeV. The angular sensitivities of the devices are studied and compared with Monte-Carlo predictions. We also present the results obtained at the HIMAC accelerator with 500 MeV/u Fe ions and at the CERN high energy radiation reference fields. Records made during airplane flights are shown and compared with the predictions of the CARI-6 model.

Effect of partition walls and neighboring buildings on the indoor exposure rate due to cosmic-ray muons.

Numerical calculations were done of the indoor exposure rate due to the cosmic rays. Only muons were considered, and the calculations were done within a two-dimensional framework under the non-scattering approximation. The effects of various structural parameters on the level and the distribution of the exposure rate were studied by a case control method. It was shown that a building's dimensions and the floor thickness were important in all cases. However, the effect of partition walls would become significant only when the partition number is large. The effect of neighboring buildings would be especially important in the lower floors of tall buildings. In such a case, attention is necessary not only to the buildings' internal structures but also to the relationship between that particular building and its neighborhood. The maximum amplitude of the possible variation of the exposure rate due to the change of any single structural parameter would be 30% in ordinary Japanese housing conditions.

Responses of TLD Mg2SiO4:Tb and radiophotoluminescent glass to heavy charged particles and space radiation.

The LET dependences of thermoluminescence dosimeters of Mg2SiO4:Tb (TLMS) and radiophotoluminescent glass dosemeters (RPLG) were examined using high energy, heavy ion beams. TLMS kept its efficiency below 10 keV micrometer-1 and decreased almost linearly with the logarithm of LET for higher LET particles. The efficiency of RPLG decreased more gradually than TLMS although its reduction was observed at a lower LET region around 0.5 keV micrometer-1. Accordingly, the ratio of TLMS to RPLG valued showed a maximum peak around 20 keV micrometer-1 of LET. The results obtained with both dosemeters in the 40 day space mission in the Russian space station Mir showed that not only dose level but also radiation quality were varying considerable in the Mir Core Module.

Efficiency of a radiophotoluminescence glass dosemeter for low-earth-orbit space radiation.

Chips of a radiophotoluminescence glass dosemeter (RPLG) were used for measurements of space radiation during a 9.8 d Shuttle-Mir mission (STS-91) at an altitude of 400 km and an inclination of 51.65 degrees. Two of RPLG chips were put into each of 59 positions in or on a life-size human phantom. The RPLG values equivalent to 137Cs gamma ray absorbed doses were found to be systematically lower than those of a Mg2SiO4:Tb thermoluminescence dosemeter (TDMS). In comparison with the organ or tissue absorbed dose and dose equivalent values that were estimated using a combination of TDMS and plastic nuclear track detectors, the efficiencies of the RPLG chips were about 80% for the water absorbed dose and about 40% for the dose equivalent. Whereas the percentage values will change during different missions, such additional information obtained from small RPLG chips is useful for improving the reliability of radiation dosimetry in space.

Responses of TLD-BeO:Na (UD-170A) to heavy ions and space radiation.

Responses of TLD-BeO:Na (UD-170A) to high-LET particles were examined with selected heavy ion beams (He, C, Ne, Ar, and Kr) at NIRS-HIMAC, and compared with TLD-Mg2SiO4:Tb (TLMS) and radiophotoluminescent glass (RPLG). The relative TL efficiency of UD-170A as 137Cs gamma ray equivalent arose notably with increasing LET infinity.H2O for He and C, and decreased for the heavier charged particles. In contrast, the efficiencies of TLMS and RPLG did not increase over the range of LET from 0.5 to 410 keV.micron-1. The three detectors were used for space radiation measurement in the Mir space station for 40 days at 400 km altitude and 51.65 degrees inclination. The values from each detector as gamma ray absorbed dose equivalent showed a large spatial variation by a factor 2 in the same Core module. The detector values were in the order of UD-170A > TLMS > RPLG as expected from the results obtained on the ground, although ratios of these values changed depending on positions. These results indicate that both radiation quality and dose level in a spacecraft change significantly and a measurement at one location cannot accurately represent the individual dose to an astronaut. These small detectors should be useful as supplementary personal dosemeters for astronauts.

Differential dosimetry in a neutron-proton mixed field with low-pressure proportional counters.

For a mixed radiation field of neutrons and protons, radiation events were discriminated between photons, neutrons, and protons using a thin plastic scintillator. Distributions of lineal energy were measured with low-pressure proportional counters (LPPCs). To estimate the distribution of lineal energy for ICRU muscle, measurements were carried out using A-150-walled, graphite-walled, ZrO2-walled, and Zr-walled counters. Data were corrected for different atomic compositions between the A-150 plastic and ICRU muscle.