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To determine the effectiveness of two UV spectra with different UVB components for cell kill and micronucleus induction in irradiated human HeLaxskin fibroblast (CGL1) hybrid cells and their progeny. To determine the presence of reactive oxygen species (ROS) in the progeny of the irradiated cells at various post-irradiation times and their relationship with induced delayed biological effects.A commercial solar ultraviolet simulator was used. Two different filters were employed: the first transmitted radiation with lambda284nm and the second radiation with lambda293nm. The resulting spectra have different UVB components (lambda between 284 and 320nm, 19 W/m(2), and between 293 and 320nm, 13 W/m(2)) and the same UVA component (lambda between 320 and 400nm, 135 W/m(2)). CGL1 cells were irradiated with various doses. Clonogenic survival and micronucleus formation were scored in the irradiated cells and their progeny. ROS were detected by incubation of cultures at various post-irradiation times with dichlorodihydrofluorescein diacetate followed by flow cytometric measurement of the final product, dichlorofluorescein.The biological effectiveness of the lambda284nm spectrum was higher by a factor of 3 compared to the lambda293nm spectrum for cell kill, and by a factor of 5 for micronucleus induction. No delayed cell death or micronucleus formation was found in the progeny of cells exposed to lambda293nm, while a large and dose-dependent effect was found in the progeny of cells exposed to lambda284nm for both of these endpoints. ROS levels above those in unirradiated controls were found only in the progeny of cells exposed to the lambda284nm spectrum.The spectrum with lambda284nm was more effective than that with lambda293nm for induction of cell kill and micronucleus formation in the directly irradiated cells as well as induction of delayed effects in the progeny in the form of delayed reproductive death and micronucleus formation. The presence of ROS in the progeny of the irradiated cells may be the cause of the delayed effects.

This work aimed at measuring cell-killing effectiveness of monoenergetic and Spread-Out Bragg Peak (SOBP) carbon-ion beams in normal and tumour cells with different radiation sensitivity. Clonogenic survival was assayed in normal and tumour human cell lines exhibiting different radiosensitivity to X- or γ-rays following exposure to monoenergetic carbon-ion beams (incident LET 13–303 keV/μm) and at various positions along the ionization curve of a therapeutic carbon-ion beam, corresponding to three dose-averaged LET (LETd) values (40, 50 and 75 keV/μm). Chinese hamster V79 cells were also used. Carbon-ioneffectiveness for cell inactivation generally increased with LET for monoenergetic beams, with the largest gain in cell-killing obtained in the cells most radioresistant to X- or γ-rays. Such an increased effectiveness in cells less responsive to low LET radiation was found also for SOBP irradiation, but the latter was less effective compared with monoenergetic ion beams of the same LET. Our data show the superior effectiveness for cell-killing exhibited by carbon-ion beams compared to lower LET radiation, particularly in tumour cells radioresistant to X- or γ-rays, hence the advantage of using such beams in radiotherapy. The observed lower effectiveness of SOBP irradiation compared to monoenergetic carbon beam irradiation argues against the radiobiological equivalence between dose-averaged LET in a point in the SOBP and the corresponding monoenergetic beams.

To determine the relative biological effectiveness (RBE) for initial and delayed inactivation of cells by a modulated proton beam suitable for the treatment of tumours of the eye, within the spread-out Bragg peak and in its distal declining edge.Human tumour SCC25 cells were irradiated with the 65 MeV proton beam at the Cyclotron Medicyc in Nice. Perspex plates of different thickness were used to simulate five positions along the beam line: 2mm corresponding to the entrance beam; 15.6 and 25 mm in the spread-out Bragg peak; 27.2 and 27.8mm for the distal edge. At each position clonogenic survival of the irradiated cells and of their progeny were determined at various dose values. 60Co gamma-rays were used as reference radiation.RBE values evaluated at the survival level given by 2 Gy of gamma-rays increased with increasing depth from close to 1.0 at the proximal to about 1.2 at the distal part of the peak. Within the declining edge it reached the value of about 1.4 at 27.2 and about 2 at 27.8 mm. For the progeny of irradiated cells, the RBE value ranged from 1.0 to 1.1 within the spread-out Bragg peak and then increased up to a value of 2.0 at the last position. The dose-effect curves for the progeny always had a larger shoulder than for the irradiated progenitors, their alpha parameters being lower by a factor of about 4 and their beta parameters always being higher. The alpha/beta ratio was about 50 Gy for the progenitors and about 6 Gy for their progeny. The incidence of delayed effects increased with dose and with the depth within the beam.RBE values for the inactivation of cells irradiated in the spread-out Bragg peak are compatible with the value currently assumed in clinical applications. In the distal declining edge of the beam, the RBE values increased significantly to an extent that may be of concern when the region of the treatment volume is close to sensitive tissues. The yield of delayed reproductive cell death was significant at each position along the beam line.

The aim of this research was to determine the biological effectiveness for early and delayed effects of high energy, high linear energy transfer (LET) charged particles. Survival and delayed reproductive death were measured in AG1522 human fibroblast cells exposed to Fe-ion beams of energies between 0.2 and 1 GeV/n, 0.97 GeV/n Ti-ion and 0.49 GeV/n Si-ion beams. The cells were irradiated at the HIMAC accelerator in Chiba, Japan (0.2 and 0.5 GeV/n Fe and 0.49 GeV/n Si) and at the NASA Space Radiation Laboratory in Brookhaven, USA (1 GeV/n Fe and 0.97 GeV/n Ti ions). The dose-effect curves were measured in the dose range between 0.25 and 2 Gy. For comparison cells were exposed to 60Co gamma rays. Analysis of the dose-effect curves show that all the heavy ion beams induce inactivation and delayed reproductive death more effectively than 60Co gamma rays. The only exception is the 0.2 GeV/n Fe-ion beam at low doses. The progeny of the irradiated cells show delayed damage in the form of reproductive death with all the heavy ion beams with the 1 GeV/n Fe-ion beam being the most effective. The relative biological effectiveness at low doses of the iron beams is highest for LET values between 140 and 200 keV/micrometers with values of 1.6 and 3 for early and delayed reproductive death, respectively. Analysis of the fluence-effect curves shows that the cross-sections for early and delayed inactivation increase with increasing LET up to 442 keV/micrometers.

Measurements of C3H10T1/2 and V79 cell thickness were performed on living cells by confocal laser fluorescence microscopy. Thickness distributions are reported for cells growing as a monolayer (on mylar and glass) and suspended in their medium. Mean values for cells grown on mylar (corrected for refractive index effects) are 2.9 +/- 0.6 and 6.1 +/- 1.0 microm for C3H10T1/2 and V79 cells respectively. Mean values of the diameters of cells suspended in their medium are 13.0 +/- 1.6 and 9.3 +/- 1.4 microm for C3H10T1/2 and V79 respectively. Knowledge of cell thickness, as irradiated, is of central relevance for studying the relative biological effectiveness of low energy, poorly penetrating radiations. It can be concluded, from the measured cell thickness distributions, that with C3H10T1/2 cells grown on mylar, the LET variation through the whole cell is within 20% for protons and alpha-particles with energies down to 0.6 and 2.5 MeV respectively. From a comparison with thickness values reported in the literature for living or fixed embedded cells growing on plastic substrate, mean values between 2.4 and 3.4 microm and between 6 and 7.5 microm could be assumed for C3H10T1/2 cells and for the most widely used V79 cell lines respectively.

Survival and oncogenic transformation frequencies were determined through the cell cycle in hybrid cells (HeLa x human skin fibroblasts), exposed to 0.30 and 0.15 Gy 4.3 MeV (LET= 101 keV/microm) alpha-particles. The cells were synchronized by mitotic collection and irradiated at times ranging from 2 to 10 h after collection, corresponding to G1 and early S. At 0.30 Gy the highest value in the transformation frequency (1.6 +/- 0.3) x 10(-4) transformants/survivor, occurred 4 h after mitotic collection, corresponding to mid-G1 and was about twice as high as that for the asynchronous population (0.7 +/- 0.1) x 10(-4) transformants/survivor. A similar pattern was seen at 0.15 Gy albeit less marked. The results are similar to previous findings with C3H10T1/2 exposed to 0.30 Gy where (1.8 +/- 0.4) x 10(-4) and (0.8 +/- 0.4) x 10(-4) transformants/survivor were found in mid-G1 and in the asynchronous population respectively. The results of both these studies with 101 keV/microm alpha particles indicate that mid-G1 cells may be more sensitive than asynchronous cells by up to a factor of two. However, it is unlikely that such a factor is sufficient to represent the cell cycle 'hot spot' for transformation postulated to explain the inverse dose-rate effect.

Within the framework of radiation biophysics research in the hadrontherapy field, split-dose studies have been performed on four human cell lines with different radiation sensitivity (SCC25, HF19, H184B5 F5-1 M10, and SQ20B). Low energy protons of about 8 and 20 keV/micron LET and gamma-rays were used to study the relationship between the recovery ratio and the radiation quality. Each cell line was irradiated with two dose values corresponding to survival levels of about 5% and 1%. The same total dose was also delivered in two equal fractions separated by 1.5, 3, and 4.5 hours. A higher maximum recovery ratio was observed for radiosensitive cell lines as compared to radioresistant cells. The recovery potential after split doses was small for slow protons, compared to low-LET radiation. These data show that radiosensitivity may not be related to a deficient recovery, and suggest a possible involvement of inducible repair mechanisms.

To analyse the cell inactivation frequencies induced by low energy protons in human cells with different sensitivity to photon radiation.Four human cell lines with various sensitivities to photon irradiation were used: the SCC25 and SQ20B derived from human epithelium tumours of the tongue and larynx, respectively, and the normal lines M/10, derived from human mammary epithelium, and HF19 derived from a lung fibroblast. The cells were irradiated with y-rays and proton beams with linear energy transfer (LET) from 7 to 33 keV/microm. Clonogenic survival was assessed.Survival curves are reported for each cell line following irradiation with gamma-rays and with various proton LETs. The surviving fraction after 2 Gy of gamma-rays was 0.72 for SQ20B cells, and 0.28-0.35 for the other cell lines. The maximum LET proton effectiveness was generally greater than that of gamma-rays. In particular there was a marked increase in beam effectiveness with increasing LET for the most resistant cells (SQ20B) whose 2 Gy-survival varied from 0.72 with gamma-radiation down to 0.37 with 30 keV/microm protons. The relative biological effectiveness (RBE(2 Gy gamma)) with the 30 keV/microm beam, evaluated as the ratio of 2 Gy to the proton dose producing the same inactivation level as that given by 2 Gy of gamma-rays, was 3.2, 1.8, 1.3 and 0.8 for SQ20B, M/10, SCC25, and HF19, respectively.RBE for inactivation with high-LET protons increased with the cellular radioresistance to gamma-rays. The cell line with the greatest resistance to gamma-rays was the most responsive to the highest LET proton beam. A similar trend has also been found in studies reported in the literature with He, C, N ions with LET in the range 20-125 keV/microm on human tumour cell lines.

There is substantial experimental evidence that protracted exposure to high-LET radiation can have a greated effect than single exposure in inducing cell transformation, the so-called «inverse dose-rate effect». The magnitude of this enhancement is due to the complex interplay between dose, dose rate and radiation quality. We have developed a model that explains the complex trend of the experimental results. This model is based on the assumption that there is a brief period of high sensitivity to transformation in the cell cycle as proposed in the literature and takes into account the saturation observed at high doses in the dose-effect curves. Specific equations are reported for acute, protracted and fractionated irradiation. Findings with C3H10T1/2 cells were analised in the light of this model. Assuming best fitted parameters of the model obtained from acute-irradiation data, tranformation frequencies due to protracted or fractionated exposure were predicted and compared with experimental findings on fission and monoenergetic neutrons and on charged particles of LET between 20 and 150 keV/μm. The model’s predictions were found to be closely consistent with the available experimental data.

In the present paper we report the realization of a mode-locked hybrid distributed Bragg reflector (HDBR) laser for picosecond optical pulse generation at 10-GHz repetition rate, 12.7-ps 2-mW optical pulses, with 400-MHz locking bandwidth have been obtained by using a saturated (95% of peak reflectivity) Gaussian Bragg grating. Linear phase gratings have shown even better results in terms of stability and output power (7 mW), whereas so far 15 ps of pulsewidth has been achieved, mainly limited by the spectral bandwidth of the grating. Key features of this realization are the intrinsic simplicity and the compactness of the laser source.

Human cell line/Carbon-ion beams/Cell inactivation/Relative Biological Effectiveness (RBE)/Linear Energy Transfer (LET). This work aimed at measuring cell-killing effectiveness of monoenergetic and Spread-Out Bragg Peak ( SOBP) carbon-ion beams in normal and tumour cells with different radiation sensitivity. Clonogenic survival was assayed in normal and tumour human cell lines exhibiting different radiosensitivity to X- or γ-rays following exposure to monoenergetic carbon-ion beams (incident LET 13–303 keV/μm) and at various positions along the ionization curve of a therapeutic carbon-ion beam, corresponding to three doseaveraged LET (LETd) values (40, 50 and 75 keV/μm). Chinese hamster V79 cells were also used. Carbon-ion effectiveness for cell inactivation generally increased with LET for monoenergetic beams, with the largest gain in cell-killing obtained in the cells most radioresistant to X- or γ-rays. Such an increased effectiveness in cells less responsive to low LET radiation was found also for SOBP irradiation, but the latter was less effective compared with monoenergetic ion beams of the same LET. Our data show the superior effectiveness for cell-killing exhibited by carbon-ion beams compared to lower LET radiation, particularly in tum our cells radioresistant to X- or γ-rays, hence the advantage of using such beams in radiotherapy. The observed lower effectiveness of SOBP irradiation compared to monoenergetic carbon beam irradiation argues against the radiobiological equivalence between dose-averaged LET in a point in the SOBP and the corresponding monoenergetic beams.

Cytotoxicity and oncogenic transformation incidence were studied in C3H 10T1/2 cells irradiated with 4.3 MeV alpha particles and were compared with results previously obtained with low LET protons. The alpha particles were more effective than low LET protons both in cell inactivation and for oncogenic transformation. The survival curve with alpha particles was an exponential function of the dose with a mean lethal dose of 0.61 ± 0.02 Gy. The corresponding RBE was a decreasing function of the dose varying from 15 to 4 when alpha particle doses ranged from 0.1 to 2 Gy. The transformation curves show complex shapes with a region of apparent constancy at low doses followed by a linear increase with dose. RBE values decreased from 20 to 4 in the dose region between 0.1 and 2 Gy. There was a significant transformation incidence at doses that have very little effect on cell survival. No effect of the dose rate was found at total doses of 0.05 and 0.1 Gy with dose rates of 0.11 and 0.005 Gy.min-1.

A hybrid source has been realized, integrating a fast Fabry-Perot laser and a fiber grating. The device has shown very good performances in the 1530-1570-nm range, obtaining 16 mA of threshold current at 20/spl deg/C, 1.6-mW fiber optical power and 48 dB of sidemode suppression ratio at 50 mA bias current. The cavity length was designed to achieve a good tradeoff between chirp reduction and increasing speed. The device has shown for the first time, to our knowledge, more than 15 GHz of small-signal modulation bandwidth, and 10-Gb/s modulation capability. Moreover, a penalty-free transmission experiment at 2.5 Gb/s over 100 km of standard fiber has confirmed the very low wavelength chirp of the device. These previous characteristics together with an extremely low temperature dependence (

We present an analysis and explanation of the presence of backreflected signal in an all-fiber bandpass transmission filter. The device is based on a 3-dB fused coupler and two Bragg gratings photoimprinted in the output arms of the coupler. Solutions to correct this problem are proposed.

(1). To determine the biological effectiveness of two solar ultraviolet (UVB) spectra with different lower wavelength thresholds for oncogenic transformation and micronucleus induction in CGL1 cells; (2). to investigate whether the action spectra for short- and long-term effects are similar; and (3). to investigate possible links between transformation and other delayed effects.Two spectra were derived from a solar UV simulator by using two filters: the first transmitted radiation with lambda284 nm, the second with lambda293 nm. The resulting spectra have the same UVA, but different UVB components (lambda between 284 and 320 nm, 19 W m(-2), and lambda between 293 and 320 nm, 13 W m(-2)). CGL1 cells were irradiated with 466 J m(-2) with lambda284 nm and 1582 J m(-2) with lambda293 nm. These doses were approximately equilethal. The endpoints examined were oncogenic transformation, and centromere-positive and -negative micronucleus frequencies in the directly irradiated cells and in transtheir progeny.At equilethal doses, the oncogenic transformation frequency in the directly irradiated cells was greater by a factor of at least 7 for lambda284 nm irradiation compared with lambda293 nm. The micronucleus induction frequency was also significantly higher with the lambda284 spectrum. Consistent with our previous findings, no delayed micronucleus formation was found in the progeny of cells exposed to lambda293 nm, while a threefold elevation above controls was seen in the progeny of cells exposed to lambda284 nm irradiation. This was also the case for formation of micronuclei with a centromere.It was found that: (1). for equilethal doses the lambda284 nm spectrum was more biologically effective than the lambda293 nm spectrum for induction of oncogenic transformation and micronucleus formation; and (2). the higher effectiveness of the lambda284 nm spectrum found at equilethal doses for delayed effects in the progeny of irradiated cells resembles that found for transformation. The results suggest that the UVB action spectrum for cell killing is different from that of some delayed effects, and from that of transformation.

We show the aspects that rule the design of a Hybrid Distributed Bragg Reflector (HDBR) package and a possible low cost solution with adhesives. We ensure single-mode behaviour in a operative range of 10/spl deg/C (17-27/spl deg/C) bending and fixing a tapered fiber to a very stable ceramic structure. The source at 1.55 /spl mu/m, suitable for direct modulation at 2.5 Gbit/s, exhibits a temperature dependence of 0.013 nm//spl deg/C (nearly one order of magnitude less than a typical DFB laser) and a static linewidth lower than 40 kHz at 1.5 mW output power, with Side Mode Suppression Ratio (SMSR) of 43 dB.

We report, for the first time, to our knowledge, the realisation of a HDBR (hybrid distributed Bragg reflector) laser for picosecond optical pulse generation at about 10 GHz repetition rate. 12.7 ps pulses, with 400 MHz locking bandwidth have been obtained.

Long-period fiber gratings can be applied in several optical devices, such as mode converters, gain equalizers for optical fiber amplifiers, and band rejection filters. In order to design long-period gratings, a mathematical model has been developed, based on the coupled-mode theory, which takes into account different refractive-index profiles of the gratings and of the fiber.

Published data on inactivation of V79 cells irradiated with monoenergetic proton and ion beams (He, C, O, Ne) have been analysed. Values for RBE alpha, RBE10% and the inactivation cross section sigma have been evaluated in the LET range between 5 and 400 keV.micron-1. RBE against LET curves and inactivation cross sections against LET and against Z*2/beta 2 curves have been studied in a comparative approach with respect to the different ion types. RBE-LET curves depend strongly on the type of ion for LET30 keV.micron-1. At LET30 keV.micron-1 and low doses protons show the greatest effectiveness; at LET30 keV.micron-1 and high doses He ions provide the most effective radiation. Apart from protons, separation among the various ion curves is less marked in the sigma against Z*2/beta 2 plot than in the sigma against LET plot. sigma against Z*2/beta 2 curves for ions with 2or = Zor = 10 and 200Z*2/beta 21500 show a common trend independent of Z and are well represented by a linear relationship.

Using a semiconductor laser with a fiber Bragg grating external cavity, 10 GHz actively mode-locked short pulses (3.8 ps) with very low timing jitter (160 fs RMS) have been generated at a wavelength of 1553 nm.

For the assessment of radiation risk at low doses, it is presumed that the shape of the low-dose-response curve in humans for cancer induction is linear. Epidemiological data alone are unlikely to ever have the statistical power needed to confirm this assumption. Another approach is to use oncogenic transformation in vitro as a surrogate for carcinogenesis in vivo. In mid-1990, six European laboratories initiated such an approach using C3H 10T1/2 mouse cells. Rigid standardisation procedures were established followed by collaborative measurements of transformation down to absorbed doses of 0.25 Gy of x-radiation resulting in a total of 759 transformed foci. The results clearly support a linear dose-response relationship for cell transformation in vitro with no evidence for a threshold dose or for an enhanced, supralinear response at doses approximately 200-300 mGy. For radiological protection this represents a large dose, and the limitations of this approach are apparent. Only by understanding the fundamental mechanisms involved in radiation carcinogenesis will further knowledge concerning the effects of low doses become available. These results will, however, help validate new biologically based models of radiation cancer risk thus providing increased confidence in the estimation of cancer risk at low doses.

Purpose To determine the RBE-LET relationship for C3H10T1/2 cell inactivation by protons in the LET range 11-33 keV/microm and to compare inactivation frequencies induced in C3H10T1/2 cells by protons and deuterons at two matching LET values in the range 11-20 keV/microm. Materials and methods C3H10T1/2 cells were irradiated with protons and deuterons at the radiobiological facility set up at the 7MV Van de Graaff accelerator at the LNL, Legnaro, Padova. Gamma rays from 60Co were used as reference radiation. Results Proton RBE values (alpha/alphagamma) for inactivation of C3H10T1/2 cells are constant around a value of 2 between 11 and 20 keV/microm and then rise sharply to reach a value of 4.2+/-1.0 at 33 keV/microm. Deuteron RBE values are 1.7+/-0.4 and 2.2+/-0.6 at LET values of 13 and 18 keV/microm respectively. Conclusions Proton RBE values with C3H10T1/2 cells are significantly larger than unity at LET values as low as 11 keV/microm. No difference in effectiveness for inactivation of C3H10T1/2 has been found between protons and deuterons at two LET values in the range 10-20 keV/microm.

Oncogenic transformation of synchronized C3H 10T1/2 cells was determined after exposure to 4.3 MeV alpha particles (LET = 101 keV/microns). Two synchronization techniques were tested using basic and modified protocols: one based on the release of cells from contact inhibition and the second on the mitotic shake-off method. Progression of cells through the cycle was followed as a function of time by flow cytometric analysis, DNA labeling for passage through S phase, the growth curve for the cell number and mitotic index measurements. The conclusion is that, although the release of cells from confluence provides higher yields of synchronized cells, mitotic shake-off proved to be the best way of collecting a synchronized population of minimally perturbed cells. Cells synchronized by mitotic shake-off were irradiated with 0.30 Gy in the interval between 2 and 10 h corresponding to G1 and early S phases. For comparison asynchronous populations were irradiated in parallel. Oncogenic transformation frequency, corrected for background, in mid-G1 phase was (18 +/- 4) x 10(-5) (average values of frequencies at 4 and 6 h) compared with the value of (8 +/- 4) x 10(-5) for the asynchronous population. While these data are suggestive of a trend toward a slightly increased sensitivity in mid-G1 phase, it is not statistically significant. The surviving fraction is constant in G1 phase.

Cell-cycle stage radiosensitivity for the induction of chromosome aberrations has been investigated in C3H 10T1/2 cells. Exponentially growing cells were irradiated with 3 Gy X-rays (80 kVp) or 0.6 Gy alpha-particles (LET = 101 keV/micron). The two doses produce the same survival level (37%) in the asynchronous population. Cells were harvested at four different times following irradiation and cell-cycle phase at the time of irradiation was assessed by using the differential replication staining technique. The frequency of chromosome aberrations produced in a given stage of the cell cycle was not constant as a function of the sampling time, but this could not be simply related to the existence of subphases exhibiting different radiosensitivity, because of cell-cycle perturbation introduced by radiation. X-radiation induced more exchanges than deletions, whereas a predominance of isochromatid deletions was observed after alpha-irradiation. This can be interpreted on the basis of the different patterns of energy deposition of densely- and sparsely-ionizing radiation. Both X- and alpha-rays produced a significant increase in the frequency of Robertsonian translocations when cells were exposed in G1 or S phase, but not in G2 phase.

Oncogenic transformation of C3H 10T1/2 cells was determined after exposure to graded doses of 4.3-MeV alpha particles LET = 101 keV/microns. The source of alpha particles was 244Cm and the irradiation was done in an irradiation chamber built for the purpose. Graded doses in the range of 0.2 to 300 cGy were studied with special emphasis on the low-dose region, with as many as seven points in the interval up to 10 cGy. The dose-effect relationship was a complex function. Transformation frequency increased with dose up to 2 cGy; it seemed to flatten at doses between 2 and 20 cGy but increased again at higher doses. A total of 21 cGy was delivered in a single dose or in 3 or 10 equal fractions at an interval of 1.5 h. An inverse dose-protraction effect of 1.4 was found with both fractionation schemes. Measurements of the mitotic index of the population immediately before the various fractions revealed a strong effect on the rate of cell division even after very low doses of radiation. Mitotic yield decreased markedly with the total dose delivered, and it was as low as 50% of the control value after 4.2 cGy and 20% after 14 cGy with both fractionation schemes.

Cell survival was studied by analyzing the inactivation probability density function and its fundamental parameters. Mean D, variance sigma 2 and mode Dmode were evaluated and a set of equations relating these parameters to the usual parameters of the multitarget, multihit and linear-quadratic models Do and n, alpha and beta, kappa and lambda are reported. The multihit equation used was an extension of the usual equation, to allow parameter kappa to assume values that are not necessarily integers. In the multitarget curve, the mode of inactivation probability density function, proved to be the quasi-threshold dose Dq = Do ln(n). Relative variance, degree of asymmetry and degree of peakedness can be calculated from the shape parameters n in the multitarget model, kappa in the multihit model, and alpha/square root of beta in the linear-quadratic model. From an analysis of eight published cell survival sets of data, on C3H10T1/2 cells exposed to low LET radiations, it was found that D, sigma, and SF2 are the parameters which exhibit the least variation from experiment to experiment and the least variation in selecting the range of data available for estimation.

Oncogenic transformation of synchronized C3H 10T1/2 cells was determined after exposure to 4.3 MeV alpha particles (LET = 101 keV/microns). Two synchronization techniques were tested using basic and modified protocols: one based on the release of cells from contact inhibition and the second on the mitotic shake-off method. Progression of cells through the cycle was followed as a function of time by flow cytometric analysis, DNA labeling for passage through S phase, the growth curve for the cell number and mitotic index measurements. The conclusion is that, although the release of cells from confluence provides higher yields of synchronized cells, mitotic shake-off proved to be the best way of collecting a synchronized population of minimally perturbed cells. Cells synchronized by mitotic shake-off were irradiated with 0.30 Gy in the interval between 2 and 10 h corresponding to G1 and early S phases. For comparison asynchronous populations were irradiated in parallel. Oncogenic transformation frequency, corrected for background, in mid-G1 phase was (18 +/- 4) x 10(-5) (average values of frequencies at 4 and 6 h) compared with the value of (8 +/- 4) x 10(-5) for the asynchronous population. While these data are suggestive of a trend toward a slightly increased sensitivity in mid-G1 phase, it is not statistically significant. The surviving fraction is constant in G1 phase.

Oncogenic transformation of C3H 10T1/2 cells was determined after exposure to graded doses of 4.3-MeV α particles LET = 101 keV/μm. The source of α particles was ${}^{244}{\rm Cm}$ and the irradiation was done in an irradiation chamber built for the purpose. Graded doses in the range of 0.2 to 300 cGy were studied with special emphasis on the low-dose region, with as many as seven points in the interval up to 10 cGy. The dose-effect relationship was a complex function. Transformation frequency increased with dose up to 2 cGy; it seemed to flatten at doses between 2 and 20 cGy but increased again at higher doses. A total of 21 cGy was delivered in a single dose or in 3 or 10 equal fractions at an interval of 1.5 h. An inverse dose-protraction effect of 1.4 was found with both fractionation schemes. Measurements of the mitotic index of the population immediately before the various fractions revealed a strong effect on the rate of cell division even after very low doses of radiation. Mit...

Transformation frequencies induced in cell systems by low- and high-LET radiations are compared and analysed as a function of LET and dose protraction. At acute dose rates, the dose-response curve with low-LET radiations shows a complex shape: the transformation frequency increases with the dose by a power of less than 1 in the interval (0.25÷1.5) Gy; a power of about 2 from 1.5 Gy to 4.5 Gy, where it reaches its maximum value and then remains constant. High-LET radiation transformation frequencies increase with dose by a power of 2 from 0.1 to 2 Gy after which they remain constant. RBE values increase with LET up to 140 ke V/μm and then decrease. The transformation frequency is reduced following dose fractionation or dose rate reduction with low-LET radiation, whereas it is enhanced with high-LET radiation, such as 0.85 MeV neutrons. Values of RBE for transformation up to 50 can be evaluated for neutrons. Various models that have been proposed to explain these results are analysed and compared.

The effects of cell density on transformation frequencies were studied in C3H10T1/2 cells exposed to 0.5 and 7 Gy of 200 kVp X-rays. Initial cell density strongly influenced transformation frequency; this decreased by a factor of between 4 and 10 when the initial seeding density was changed from 50 to 2500 cells/10 cm diameter Petri dish. The data were fitted with two equations: (a) an allometric function represented on a log-log scale by a straight line and (b) a sigmoidal function with plateaux between 50 and 250 cells/dish and above 600. The two curves are compared and their probabilities discussed. Our data indicate that the region between 50 and 250 cells/dish would be the most suitable region for dose-effect measurements. A study of the growth curves at 0.5 and 8.5 Gy shows that cell growth rates are not influenced by initial cell density.

Chromosome aberrations were induced in cultured human cells by proton beams of 31, 12, and 8 MeV. The frequencies of isochromatid breaks and dicentrics have been analysed as a function of proton energy and dose. Both effects are largely dependent on proton energy; isochromatid breaks increased linearly with the dose, whereas dicentrics show a definite parabolic behaviour. The experimental data were fitted to the analytic form Y = KDn and Y = alpha D + beta D2 and the best fitted values of the parameters are reported and discussed. The values of RBE for the isochromatid breaks are in the ratio 1.7:1.3:1 for 8, 12, and 31 MeV respectively. In the case of the dicentrics the RBE values are dose-dependent function of the type CD-n. The three distributions of dicentrics among the cells do not fit a Poisson distribution.

We present results on annihilations of antiprotons at 1.2 GeV/c into two-, three- and four-body final states including at least one visible K 1 0 . The three- and four-body channels are dominaned by K*(891). Resonances in the\(K\bar K\) and\(K\bar K\pi \) systems are discussed and cross-sections are given. It is found that at 1.2 GeV/c it is no longer true that annihilation occurs predominantly fromS-states.

Elastic scattering, single-pion and deuteron production have been investigated. The cross-section for elastic scattering is σelastic = (13.5±0.3) mb. The angular distribution has been fitted to dσ/d|t|=(dσ/d|t|)0 e −bt in the region of low values oft. The best fit givesb=(6.7±0.5) (GeV/c)−2 and (dσ/d|t|)0=(91±5) mb(GeV/c)−2. The cross-sections for ppπ0, pnπ+ reactions are respectively (2.6±0.3) mb and (9.7±0.4) mb. These reactions are dominated by the (3/2, 3/2) nucleonpion isobar production and by forward backward collimation of the nucleons. The production rates for the isobars $$\mathcal{N}_{1238}^{ * + + } $$ , $$ \mathcal{N}_{1238}^{ * + } $$ , $$\mathcal{N}_{1500}^{ * + } $$ have been estimated, taking into account the experimental peripheral behaviour of the interaction. In the pnπ+ reaction they are (50±2)%; (10±3)%; (4±3)%. In the ppπ+ reaction the production of $$\mathcal{N}_{1238}^{ * + + } $$ is estimated to be (45±10)%. The dπ+ and dπ+π+π- reaction cross-sections are respectively (0.03±0.01) mb, and (0.04±0.01) mb.

In a stack of striped emulsions three cases of K-meson decays have been found. K2 and K3 have a mass of 915±130 m3e; the secondaries cannot be identified. The mass of K1-meson is 1020±270 me (scattering-range) and 1165±130 me (ionization-range); its secondary is a light meson withpβ= 104±24 MeV/c.