Radiation research. Supplement最新文献

With confluent cultures of the C3H10T1/2 mammalian cell line, we have investigated the effects of heavy-ion radiation on neoplastic cell transformation. Our quantitative data obtained with high-energy carbon, neon, silicon, argon, iron, and uranium particles show that RBE is both dose- and LET-dependent for malignant cell transformation. RBE is higher at lower doses. There is an increase of RBE with LET, up to about 100-200 keV/micron, and a decrease of RBE with beams of higher LET values. Transformation lesions induced by heavy particles with LET values greater than 100 keV/micron may not be repairable in nonproliferating cells. RBE for slow and nonproliferating cells may be much higher than for actively growing cells.

Biological phenomena related to the inactivation of eukaryotic cells by noxious agents have been formulated mathematically in the repair-misrepair (RMR) model by separately quantitating the initial submicroscopic production of molecular lesions and the later, macroscopic expression of effects in the course of cell progression and repair. This paper presents some conceptual and quantitative similarities and differences between the RMR and seven other models proposed for cellular radiobiology including: the linear-quadratic, three-lambda, cubic-survival, target theory, hit-size probability, cybernetic, and lethal-potentially lethal models. The comparison of the various approaches has shown that the RMR model can be generalized to show relationships with each.

Induced rearrangements of chromosomes, disrupting the orderly sequence and/or separation of the genetic material, are responsible for a significant proportion of cellular lethality, genetic mutation, and, as has become increasingly apparent in recent years, human cancer. The quantitative observation of chromosomal aberrations induced by ionizing radiations led early to the realization that as linear energy transfer (LET) increased, curvilinear dose responses became increasingly linear. Those few studies that examined aberrations as a function of LET found that the optimally effective LET was about 100 keV per micrometer, results consistent with those observed for other end points. The majority of chromosomal aberrations originate from molecular interaction between pairs of lesions (misrepair), with differences in sensitivity to aberration induction through the cell cycle. In Chinese hamster V-79 cells for all LET values studied, aberrations are most frequent in G2, then G1, then S phase of the cell cycle. The variation in sensitivity through the cell cycle changes from a factor of about 5 for 10 keV/micron particles to about 3 for 80 keV/micron particles. In the G2 phase a curvilinear dose response (G1 and S being linear) is found for all LETs occurring at fluences where there are substantial distances (greater than or equal to 3 micron) between particles. It is possible that for this one phase of the cell cycle a saturation of repair capabilities occurs as a function of both fluence and LET. When cells were irradiated with associated charged particles (molecular ions) it was found that even when two particles were separated by distances of less than 100 nm their effect was much less than one particle of twice the LET (the equivalent of 0 distance separation). This implies that the vast majority of molecular interactions which result in chromosomal aberrations occur as a consequence of interaction between damaged sites formed only a few nanometers from each other. It is clear that an analysis of chromosomal aberrations produced by charged particles can provide considerable insight into basic radiobiological mechanisms and into the organization of the mammalian genome.

In track segment experiments, the inactivation of different mammalian cells by heavy charged particles between helium and uranium in the energy range between 1 and 1000 MeV/u has been measured at the heavy ion accelerator Unilac, Darmstadt, the Tandem Van de Graaf, Heidelberg, and the Bevalac, Berkeley. The inactivation cross sections calculated from the final slope of the dose-effect curves are given as a function of the particle energy and the linear energy transfer.

In the fields of high-LET radiotherapy and space radiation safety it is important to know the relative probabilities with which a cell whose nucleus is struck by a heavy ion will be damaged or killed. Experiments were performed in which synchronous cultured human T-1 cells (presumptive HeLa) were irradiated with natural alpha particles of energy approximately 3.5 MeV at various times after mitotic selection up to the middle of S phase. Nuclear-area histograms were determined as a function of time after mitosis under conditions identical to those used for irradiation. The efficiency with which one particle passing through the nucleus killed a cell was found to be 0.14-0.20. This value was extrapolated to experimental cell survival data obtained when asynchronous cultured human cells were irradiated with He, Li, B, C, N, O, Ne, Ar ions of energy 6.58 or 5.5 MeV/amu, and the cell killing efficiency was found to be in the broad range of 0.5-1.0 under single-hit conditions. Similarly irradiated cells were examined for colony-size distribution by an image analysis technique, and it was found that the loss of large colonies was dose and LET-dependent in a systematic way. Dose-response data suggest two predominant subpopulations, resistant and sensitive cells, and it appears that the sensitive population is affected by single-hit kinetics. The single-hit coefficient for the induction of inherited slow growth varied with LET in a similar way to that for survival. The action cross section for this form of heritable damage appears to be comparable to the geometric cross section of the cell nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Pi-meson experiments with repair-deficient spermatides and oocytes of Drosophila melanogaster have permitted a study of the LET dependence of the repair of different types of chromosomal lesions. The data show a distinction between primary events connected with fusion modalities (repair or misrepair) and those associated with no fusion. Repair deficiency increases the induction of chromosomal loss and dominant lethality (early damage) and decreases the induction of translocations (misrepair), perhaps responsible for late effects. The induction of nonfusion events is higher for pions compared to X rays and increases with mean lineal energy spectra, whereas the production of translocations is maximal at intermediate ionization density. The direct damage of repair systems by high-LET pions is postulated to explain these observations.

Phase I and II radiotherapy trials with accelerated high-energy heavy charged-particle beams have been carried out at the University of California Lawrence Berkeley Laboratory in conjunction with the Northern California Oncology Group and the Radiation Therapy Oncology Group. Clinical experience with several anatomical regions and tumor types has been accumulated. Preliminary observations suggest that toxicity is acceptable with treatment techniques developed for neon ions. Further data must be accumulated for carbon or silicon ion therapy. Initial Phase III trials with neon ions should begin shortly; evaluation of optimal ions and techniques for improved dose localization is ongoing. Future directions for optimization of heavy charged-particle radiotherapy are presented.