The RBE of 3.4 MeV alpha-particles and 0.565 MeV neutrons relative to 60Co gamma-rays for neoplastic transformation of human hybrid cells and the impact of culture conditions.

The neoplastic transformation of human hybrid CGL1 cells is affected by perturbations from external influences such as serum batch and concentration, the number of medium changes during the 21-day expression period and cell seeding density. Nevertheless, for doses up to 1.5 Gy, published transformation frequencies for low linear energy transfer (LET) radiations (gamma-rays, MeV electrons or photons) are in good agreement, whereas for higher doses larger variations are reported. The (60)Co gamma-ray data here for doses up to 1.5 Gy, using a low-yield serum batch and only one medium change, are in agreement with published frequencies of neoplastic transformation of human hybrid cells. For 3.4 MeV alpha-particles (LET = 124 keV/mum) and 0.565 MeV monoenergetic neutrons relative to low doses of (60)Co gamma-rays, a maximum relative biological effectiveness (RBE(M)) of 2.8 +/- 0.2 and 1.5 +/- 0.2, respectively, was calculated. Surprisingly, at higher doses of (60)Co gamma-rays lower frequencies of neoplastic transformation were observed. This non-monotonic dose relationship for neoplastic transformation by (60)Co gamma-rays is likely due to the lack of a G2/M arrest observed at low doses resulting in higher transformation frequencies per dose, whereas the lower frequencies per dose observed for higher doses are likely related to the induction of a G2/M arrest.

Dosimetry with a transportable water calorimeter in neutron, proton and heavy-ion radiation fields.

A compact and transportable water calorimeter has been developed and extensively tested in the intensive, collimated neutron field of the PTB. It has been applied for absorbed dose to water measurements in the neutron therapy field of the University of Essen, in the proton therapy fields of the HMI in Berlin and at the iThemba therapy centre near Cape Town, South Africa, as well as in the (12)C-beam of the therapy facility at GSI in Darmstadt, Germany. Absolute dosimetry with relative standard uncertainties of less than 1.8% was achieved in all radiation fields. The results obtained using the water calorimeter are compared with the ionisation chamber measurements in the same radiation fields. The heat defect for the water in the calorimeter core was determined separately in independent measurements by irradiation with different charged particle beams covering a wide range of linear energy transfer.

Absorbed dose to water determination with ionization chamber dosimetry and calorimetry in restricted neutron, photon, proton and heavy-ion radiation fields.

Absolute dose measurements with a transportable water calorimeter and ionization chambers were performed at a water depth of 20 mm in four different types of radiation fields, for a collimated (60)Co photon beam, for a collimated neutron beam with a fluence-averaged mean energy of 5.25 MeV, for collimated proton beams with mean energies of 36 MeV and 182 MeV at the measuring position, and for a (12)C ion beam in a scanned mode with an energy per atomic mass of 430 MeV u(-1). The ionization chambers actually used were calibrated in units of air kerma in the photon reference field of the PTB and in units of absorbed dose to water for a Farmer-type chamber at GSI. The absorbed dose to water inferred from calorimetry was compared with the dose derived from ionometry by applying the radiation-field-dependent parameters. For neutrons, the quantities of the ICRU Report 45, for protons the quantities of the ICRU Report 59 and for the (12)C ion beam, the recommended values of the International Atomic Energy Agency (IAEA) protocol (TRS 398) were applied. The mean values of the absolute absorbed dose to water obtained with these two independent methods agreed within the standard uncertainty (k = 1) of 1.8% for calorimetry and of 3.0% for ionometry for all types and energies of the radiation beams used in this comparison.

Influence of mitotic delay on the results of biological dosimetry for high doses of ionizing radiation.

The purpose of this study was to systematically investigate how high doses of sparsely and densely ionizing radiations influence the proliferation time of lymphocytes in short-term cultures and, consequently, the observed frequencies of dicentric and centric ring chromosomes. Peripheral blood samples from five volunteers were irradiated with high doses of 200 kV X-rays and with neutrons with a mean energy of or=2.1 MeV. First division metaphase cells were collected after different culture times of 48, 56, and 72 h and dicentrics, centric ring chromosomes, and acentric fragments were determined. The data hint at considerable mitotic delay. The main increase in the number of chromosome aberrations occurred between 48 and 72 h after an X-ray exposure and between 56 and 72 h after neutron exposure. When the data were used for a calibration of aberration frequency versus dose, subsequent dose estimations resulted, however, in comparable values. Thus, in spite of the influence of mitotic delay on observable chromosome aberrations, at least for the radiation types investigated here, a culture time of 48 h is acceptable for biological dosimetry.

Absolute dosimetry in a d(14 MeV) + Be fast neutron beam.

Since 1978, the Universitätsklinikum in Essen operates a d(14 MeV) + Be fast neutron beam for patient treatment. Dosimetric studies were performed in a rectangular 40 x 40 mm2 neutron/photon field using a transportable water calorimeter, which had been developed at the Physikalisch-Technische Bundesanstalt. The water calorimeter allowed small dosimeters to be directly calibrated in units of absorbed dose-to-water in a cylindrical phantom of 50 mm in diameter. Also, the twin detector method was applied in order to determine the photon and the neutron dose separately. By making use of a calibrated ionization chamber, the absorbed dose-to-water calibration in the cylindrical water phantom was transferred to a water phantom, a cube 300 mm on a side. Experiments and Monte Carlo calculations covering the neutron producing target, the collimator and the influence of the water calorimeter on the spectral neutron fluence at the measurement position allow the relative uncertainty of the absorbed dose-to-water determination to be reduced to 2.6% (1 SD). This direct absorbed dose-to-water determination by calorimetry has shown that the treatment planning system underestimates the physical dose to tissue by 9%. For clinical purposes, the statement of the prescribed dose had to be increased by 9% in order that the absolute absorbed dose remains constant and that the same biological endpoints are reached.

Mutagenic effect of low energy neutrons on human chromosome 11.

PURPOSE: The shape of the dose-effect curve for neutrons, i.e. the question as to whether the curve is linear or supralinear in the low-dose region, is still not clear. Therefore, the mutagenic effect of very low doses of low-energy neutrons was determined. MATERIALS AND METHODS: Human-hamster hybrid A(L) cells contain human chromosome 11, which expresses the membrane protein CD59. This membrane protein can be detected immunologically and quantified by flow cytometry. The A(L) cells were irradiated with neutrons of 0.565, 2.5 or 14.8 MeV and the results were compared with those after 200 kVp X-rays. Before irradiation, cells spontaneously mutated in the CD59 gene were removed by magnetic cell sorting (MACS). RESULTS: The relative biological effectiveness (RBE) for CD59 mutation induction was 19.8 (+/-2.7) for 0.565 MeV, 10.2 (+/-1.9) for 2.5 MeV, and 10.2 (+/-1.6) for 14.8 MeV neutrons. Linear mutation responses were obtained with all radiations except for 14.8 MeV neutrons where a supralinear curve may be a better fit. The deletion spectrum of mutated cell clones showed 29 Mbp deletions on average after irradiation with 0.069 Gy of 0.565 MeV neutrons. This scale of deletions is similar to that after 3 Gy 100 kV X-rays (=34 Mbp). For 50% cell survival, the RBE of the neutrons was 11 compared with 200 kV X-rays. CONCLUSIONS: Neutrons of low energies (0.565 or 2.5 MeV) produce a linear dose-response for mutation in the tested dose range of 0.015-0.15 Gy. The neutron curve of 14.8 MeV can be approximated by a curvilinear or linear function.

Experimental kerma coefficients and dose distributions of C, N, O, Mg, Al, Si, Fe, Zr, A-150 plastic, Al203, AlN, SiO2 and ZrO2 for neutron energies up to 66 MeV.

Low-pressure proportional counters (LPPCs) with walls made from the elements C, Mg, Al, Si, Fe and Zr and from the chemical compounds A-150 plastic, AlN, Al2O3, SiO2 and ZrO2 were used to measure neutron fluence-to-kerma conversion coefficients at energies up to 66 MeV. The LPPCs served to measure the absorbed dose deposited in the gas of a cavity surrounded by the counter walls that could be converted to the absorbed dose to the wall on the basis of the Bragg-Gray cavity theory. Numerically the absorbed doses to the walls were almost equal to the corresponding kerma values of the wall materials. The neutron fluence was determined by various experimental methods based on the reference cross sections of the 1H(n, p) scattering and/or the 238U(n, f) reactions. The measurements were performed in monoenergetic neutron fields of energies of 5 MeV, 8 MeV, 15 MeV and 17 MeV and in polyenergetic neutron beams with prominent peaks of energies of 34 MeV, 44 MeV and 66 MeV. For the measurements in the polyenergetic neutron beams, significant corrections for the contributions of the non peak energy neutrons were applied. The fluence-to kerma conversion coefficients of N and O were determined using the difference technique applied with matched pairs of LPPCs made from a chemical compound and a pure element. This paper reports experimental fluence-to-kerma conversion coefficient values of eight elements and four compounds measured for seven neutron energies, and presents a comparison with data from previous measurements and theoretical predictions. The distributions of the absorbed dose as a function of the lineal energy were measured for monoenergetic neutrons or, for polyenergetic neutron fields, deduced by applying iterative unfolding procedures in order to subtract the contributions from non-peak energy neutrons. The dose distributions provide insight into the neutron interaction processes.

Induction of DNA double-strand breaks in mammalian cells and yeast.

Induction of DNA double-strand breaks (dsb) and their distribution are dependent on the energy deposition pattern within the cell nucleus (physical structure) and the ultrastructure of the chromosomes and its variation by the cell cycle and gene activities (biological structure). For electron radiation very similar RBE-values are observed for mammalian and yeast cells (AlK, 1.5 keV, 15 keV/micrometer: 2.6 in mammalian cells and 2.2 in yeast; CK 0.278 keV, 23 keV/micrometer: approx. 2.5 in mammalian cells and 3.8 in yeast). In contrast, the RBE-values for the induction of dsb of 4He2+ and light ions in the LET range from about 100 keV/micrometer up to 1000 keV/micrometer are significantly higher for yeast cells compared to mammalian cells. For example, the RBE-value of alpha-particles (120 keV/micrometer) is about 1.2 for mammalian cells whereas for yeast the RBE-value is about 2.5. The yeast chromatin has less condensed fibres compared with mammalian cells. Since a single CK photoelectron can induce only one dsb, the different condensation of the mammalian and yeast chromatin has no influence. However, particles may induce more than one dsb when traversing a chromatin fibre. The probability for the induction of closely neighboured dsb is higher the more condensed the chromatin fibres are. Since small DNA fragments (50 bp up to several kbp) are lost by standard methods of lysis, the underestimation of dsb yields increases with fibre condensation, which is in accordance with the observes dsb yields in mammalian cells and yeast. In order to obtain relevant yields of dsb (and corresponding RBE-values) the measurement of all DNA fragments down to about 50 bp are needed.

Induction of DNA double-strand breaks by 1H and 4He lons in primary human skin fibroblasts in the LET range of 8 to 124 keV/microm.

Yields of DNA double-strand breaks were determined in primary human skin fibroblasts exposed to 1H and 4He ions at various linear energy transfers (LETs) and to 15 MeV electrons as the reference radiation. The values obtained for the relative biological effectiveness (RBE) were 2.03, 1.45 and 1.36 for 1H ions at LETs of 35, 23 and 7.9 keV/microm, respectively, and 1.2, 1.18, 1.38 and 1.31 for 4He ions at LETs of 124, 76, 35 and 27 keV/microm, respectively. The data were obtained using pulsed-field gel electrophoresis of DNA released from cells using the chromosomes of the yeast Saccharomyces cerevisiae as length markers and fitting the experimental mass distributions of fragmented DNA to those obtained by computer simulation of the random breakage of human chromosomes. The RBE values for induction of DSBs in mammalian cells cannot be fitted to a common RBE-LET relationship for electrons and 1H, 4He and light ions. Comparison of the RBEs for mammalian cells with the corresponding RBEs obtained for yeast cells shows similar RBEs of electrons for yeast and mammalian cells; however, for 4He and light ions in the LET range of 100 to 1000 keV/microm, the RBEs for yeast are significantly higher compared with mammalian cells. These characteristics of the RBE-LET relationships for yeast and mammalian cells are attributed to the fraction of small DNA fragments induced by particles when traversing the higher-order chromatin structures which are different to some extent in these two cell types.

Influence of cavity size on the response of cavity chambers to 25- and 45-MeV neutrons.

We calculated the response of gas-cavity dosimeters to 25- and 45-MeV neutrons in order to estimate the portion of the response that originates from neutron interactions within the gas cavity. This affords insight into the validity of the Bragg-Gray theory for dosimeters with finite cavities and also provides a basis for modifying gas-to-wall absorbed dose conversion factors deduced from the Bragg-Gray theory for use with small-cavity dosimeters. For a typical ionization chamber, e.g., with a 1-cm3 propane-based tissue-equivalent gas at standard temperature and pressure, the fraction of the total absorbed dose to the gas cavity from neutron interactions within the gas is 0.09% at 25-MeV and 0.006% at 45-MeV neutron energies. For microdosimetric detectors, the neutron interactions within the gas are negligible above 25 MeV.

Determination of absorbed dose within an A150 plastic phantom for a d(13.5 MeV) + Be neutron source.

In the collimated beam of a d(13.35 MeV) + Be neutron source the total absorbed dose within an A150 plastic phantom was determined using three independent methods: the twin-detector method, measurements with a tissue-equivalent calorimeter and a Monte Carlo calculation of the spectral neutron fluence within the phantom. The front of the cubic phantom was positioned at a distance of 800 mm from the neutron source. the absorbed dose data obtained by the three methods at phantom depths of 27 and 52 mm are consistent within their uncertainties. Between phantom depths of 10 and 60 mm a mean dose gradient of (1.61 +/- 0.02) Gy C-1 mm-1 has been derived.