Spatial distribution of biological effect n a 3.9-Gev nitrogen ion beam.

A beam of nitrogen ions obtained with the Princeton Particle Accelerator was used for the irradiation of Chinese hamster (M3-1) cells in monolayer culture. The 3.9-billion-electron-volt (Gev) beam passed along the monolayer, so that ions were stopped in the culture. A sharply defined zone of extensive cell destruction occurred in the last centimeter of the beam path.

Boron neutron capture enhancement of 252Cf brachytherapy.

Dosimetric and radiobiological studies were undertaken to investigate the potential enhancement in dose, dose distribution and cell killing effectiveness of 252Cf brachytherapy achievable when boron-10 enriched compounds are incorporated into simulated 252Cf brain implants. Thermal neutron distributions in a human head phantom containing a 252Cf source were measured by gold foil activation and calculated using a 1-dimensional transport code. This information was then used to modify measured event size distributions for 252Cf neutrons to determine the corresponding increase in dose and dose equivalent throughout the phantom. The addition of subtoxic levels of boron-10 to a typical 252Cf implant was found to significantly enhance both the absorbed dose and the high LET event frequency at distances of 3 to 5 cm from individual sources. Some unexpected geometric considerations are discussed. Reduced survival of cultured Chinese hamster cells correlated with the predicted increase in absorbed dose from the capture events with a concentration of about 60 micrograms 10B per ml in the culture medium. It was found that boron increased alpha (the "single-hit" parameter of the linear quadratic survival model) by 32% and decreased beta (the "double-hit" parameter) by 8%. The alpha/beta ratio increased to 4.34 Gy in the presence of boron, from 3.03 Gy in its absence. This translated to an 8% reduction in californium dose needed to effect 10% cell survival. It is concluded that there is a sufficiently high thermal neutron fluence present during californium brachytherapy for boron neutron capture dose augmentation to be feasible.

Therapeutic dosimetry for Cf-252 neutron brachytherapy of pelvic cancer.

252Cf (Cf) was used to treat tumors of the cervix and uterus with neutron brachytherapy (NT) in an ongoing clinical trial. Tandem and ovoids insertions were used and combinations of single and multiple applications along with high dose whole pelvic irradiation. Dosimetric analysis of treated cases for patterns of tissue dose were carried out. Tissue dose for Cf-NT was, in general, high for neutron components in the central pelvis only, and fell off rapidly with distance from the applicators. The majority and balance of therapeutic dose was contributed by low linear energy transfer (LET) high energy photon beam radiation to the whole pelvis. Comparison with fast neutron beam therapy (NBT) isodose curves showed that much more homogeneous neutron dose was delivered to the pelvic tumor and organs by NBT. Complication frequency has been reported to be higher for neutron beam therapy than for Cf-NT. It appears that the higher integral neutron biological dose to normal tissues for NBT compared to intracavitary Cf-NT probably contributed to the frequency of side effects.

Basic radiobiological investigations of fast neutrons.

The radiobiological properties of a cyclotron-produced 43-MeV (p----Be) fast-neutron beam relative to gamma rays have been investigated using Chinese hamster V79 cells in culture. As expected, the relative biological effectiveness (RBE) of this neutron beam for cell killing was shown to increase as dose decreased, and the effectiveness per unit dose was slightly less compared to a 25-MeV (d----Be) neutron beam. By tracing single cells that formed microcolonies after irradiation, we found cell proliferation kinetics to be retarded to a greater extent by fast neutrons than by gamma irradiation. Following either neutron or gamma irradiation, a fraction of the irradiated cells failed to divide in the first postirradiation division and another fraction could produce as many as four generations of progeny before proliferation stopped. The properties of these cells presumed to be destined for death suggest that more than one mechanism and/or multistep process underlies the radiation-induced proliferative death. The fast-neutron beam was also found to be more effective quantitatively than gamma rays in producing DNA double-strand breaks (DSBs, measured by nondenaturing filter elution), and G1-phase chromosome fragments (measured by the premature chromosome condensation technique). However, the reverse was observed for DNA single-strand breaks (SSBs, measured by alkaline filter elution or hydroxylapatite uncoiling). Interestingly, both fast neutrons and gamma rays produced a large component of SSBs and DSBs with a fast-rejoining time constant of about 2-5 min, which appears to be independent of dose. The latter results could not resolve the possibility of lengthening the repair-time constant by increasing radiation dose within the range that is reflected by the shoulder of the survival curve, and consequently did not support the idea of repair saturation as a mechanism for the presence of the shoulder. The RBE for the hypoxanthine phosphoribosyl transferase mutation frequency per survivor at the 10% survival level was estimated to be 2.5, a value that is comparable to the RBE (2.1) for cell killing at the same survival level. Although most of the above-mentioned findings are compatible qualitatively with the relatively high-LET (linear energy transfer) nature associated with the fast-neutron beam, the significance of the action attributable to the mixture of LET could not be delineated in these experiments. Further, the biological significance of DSBs and chromosome aberration and the molecular mechanisms responsible for the repair and expression of these damaging processes remain to be elucidated.

A generic off-axis energy correction for linac photon beam dosimetry.

Cooperative clinical trial group protocols frequently require off-axis point dose calculations. The Radiological Physics Center uses the calculative technique developed by Hanson et al. [Med. Phys. 7, 145-146 (1980); 7, 147-150 (1980)] to verify these calculations. In order to correct for off-axis energy changes, this technique requires off-axis half-value layer data, HVL, as a function of off-axis ray angle for the specific beam. This paper presents a formulism based on HVL mesurements on a limited number of therapy beams, which allows the calculation of an off-axis energy-correction factor for any clinical photon beam created by a linear accelerator using conventional flattening filters.

Survival-related DNA repair phenomena in cultured rat-kangaroo cells.

Cultured cells (line PtK-2) from the marsupial mammal rat-kangaroo, or potoroo (Potorous tridactylis), which photoreactivate (PR) both UV-induced dimers and lethality, excise few dimers, and are only slightly sensitized by post-UV exposure to caffeine, were subjected to caffeine and hydroxyurea (HU) treatments during the 30-min PR period. It was found that neither caffeine nor HU inhibited PR of lethality as measured by colony-forming ability. Further, the cells exhibited no photoprotective properties and 3 mM caffeine potentiated the same slight survival decrease in both photoreactivated and unphotoreactivated cells. It is evident that caffeine does not inhibit PR or the survival-related dark repair systems to any great extent, and hence the caffeine-sensitive post-UV dark repair found in this (and possibly other) mammalian cell lines may not be related directly to survival-dependent pyrimidine dimer removal, but instead to lesions or repair processes other than, but not excluding, pyrimidine dimers.

Potentiation by caffeine of ultraviolet-light damage in cultured human cells.

Five cultured human cell lines (T-1 kidney, Chang liver, H.Ep. No. 2, HeLa-S3 and HeLa-O) were irradiated with ultraviolet light and immediately exposed to 1.0 and 3.0 mM caffeine for 44 h thereafter. This caffeine treatment reduced the surviving fraction (assayed by colony formation) of the irradiated population, but did not significantly reduce the colony-forming ability of unirradiated control cells. These findings suggest that many cultured human cell lines exhibit post-UV potentiation of potentially lethal damage by caffeine.

Cellular effects of heavy charged particles.

The human cell is rendered reproductively inactive by the passage of a single heavy ion through its nucleus when the heavy ion deposits energy at a rate greater than about 3500 MeV cm-1. This is demonstrated by the correlation of inactivation probability with nuclear area when cells having nuclei of different sizes are compared. This single-hit inactivation is irreversible and unmodifiable. The ion path length over which cells will be inactivated in this way is calculable from stopping power theory. Laboratory experiments in which three-dimensional human cell cultures were irradiated with high-energy nitrogen ions (3.9 GeV) at the Princeton Particle Accelerator confirm that cells are inactivated with maximum probability over the last 0.5 cm of the ion trajectory. This means that groups of adjacent cells in the ion path will be inactivated by a single ion with high probability. Organized systems of multiplying cells would be expected to amplify this spatially correlated effect of heavy ion irradiation. Abnormalities induced in Zea seedlings by heavy ion irradiation of seeds are consistent with the inactivation of embryonic cells in groups.

Survival responses and potentially lethal damage repair of normal 10T1/2 and its transformed TCL 15 cells after irradiation with 43 MeV proton produced neutrons.

Normal 10T1/2 fibroblasts and their transformed counterparts (TCL 15) were used in order to evaluate the RBE, TGF and PLD repair for a therapeutic fast neutron beam (43 MeV proton----Be). For plateau-phase culture, the RBE of 10T1/2 cells were 2.0 and 1.7 at 10 and 1% survival levels respectively and 1.3 from D0. The corresponding RBE values of TCL 15 cells were 2.1, 1.8 and 1.5, and thus the TGF values were 1.05 and 1.1 respectively at 10% and 1% survival levels and 1.8 from D0. For log-phase culture, the survival responses of 10T1/2 and TCL 15 cells to 60Co gamma-rays or neutrons were not significantly different (the RBE at 10% was 2), and thus the TGF value was unity. For neutrons, as a rule no PLD repair has been reported in vitro and in vivo in previous studies. However, in the present study PLD repair occurred in plateau 10T1/2 and TCL 15 cells irradiated with neutrons.