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PubMedDate not supplied

[Dependence of the radiosensitivity of yeast cells on radiation LET. A theoretical analysis].

A model is proposed for interpreting the radiosensitivity of yeast cells as a function of linear energy transfer (LET) of ionizing radiation. The model takes into account the role of repair processes in sensitivity of yeast cells to ionizing radiation of different LET. Two types of repair are discussed: (1) a nonspecific repair (characteristic of both haploid and diploid cells), and (2) a diploid-specific repair (characteristic of diploid cells only).

DNA Repair↗

PubMed1987

Radial dose distribution for 18.3 MeV/n alpha beams in tissue-equivalent gas.

Experimental measurements of the radial restricted linear energy transfer (LETr) for alpha beams of 18.3 MeV/n in tissue-equivalent gas were presented. The radial dose distribution for the alpha beam was deduced from the restricted LET measurements. A differential W value for the alpha particle in the tissue-equivalent gas was also deduced. The result for the differential W value was 29.0 +/- 0.9 eV/ion pair. The radial dose varied according to an inverse-square function with distance from the track center for radii larger than 0.026 micron. The maximum extension of the track, the penumbra radius, as 2.73 +/- 1.67 microns, which was less than predicted by calculations (7-9 microns).

Alpha Particles↗

PubMed1987

The relative biological effectiveness of 670 MeV/A neon as a function of depth in water for a tissue model.

Linear energy transfer (LET infinity) spectra of identified charge fragments and primaries, produced by nuclear interactions of 670 MeV/A neon in water, were measured along the unmodulated Bragg curve of the neon beam. The relative biological effectiveness (RBE) values for spermatogonial cell killing, as reported on the basis of weight loss assay of mouse testes irradiated with beams of approximately constant single LET infinity, were summed over the particle LET infinity spectra to obtain an effective RBE for each charged-particle species, as a function of water absorber thickness. The resultant values of effective RBE were combined to obtain an effective RBE for the mixed radiation field. The RBE calculated in this way was compared with experimental RBEs obtained for spermatogonial cell killing in the mixed radiation field produced by neon ions traversing a thick water absorber. Discrepancies of 10-40% were observed between the calculated RBE and the RBE measured in the mixed radiation field. Part of this discrepancy can be attributed to undetected low-Z fragments, whose contribution is not included in the calculation, leading to an overestimated value for the calculated RBE. On the other hand, calculated values 10% greater than the measured RBE are explained as track structure effects due to the higher radial ionization density near neon tracks relative to the ionization density near the silicon tracks used to fit the RBE vs LET infinity data.

Animals↗

PubMedDate not supplied

[Lethal action of accelerated heavy ions on mammalian cells as affected by inhibitors of DNA synthesis. A theoretical analysis].

Günter-Schulz's model and the authors' own model were used to study the dependence of radiosensitivity (D0(-1)) of Chinese hamster cells on linear energy transfer (LET) upon irradiation in standard conditions and in the presence of DNA synthesis inhibitors, arabinosylcytosine and hydroxyurea. A better agreement of the experimental and theoretical results was obtained using Kozubek-Krasavin's model than the model of Günter and Schulz.

Animals↗

PubMed1987

A histological study on the cataractogenic effects of heavy charged particles.

The morphology of the mouse lens was studied by light and electron microscopy between 4 and 30 months after graded single doses of photons or charged particle exposure. Four-month-old mice were given upper body or head only doses of 220 kVp x-rays or to 40Ar (570 MeV/amu), 40Ar(500 MeV/amu), 20Ne(470 MeV/amu) and 12C (400 MeV/amu) particles. The lenses examined in this pilot study were largely from mice dedicated to other designed experiments; nor all radiation conditions are represented at each sample time. At 4 months after 0.05, 0.3 or 0.9 Gy 20Ne radiation, the micronuclei appeared in the epithelial cells at the bow region. The anterior fibers showed swollen cytoplasm containing amphorous materials after 0.3 or 0.9 Gy 20Ne exposure. The posterior fibers were relatively normal. The results at 15 months after irradiation indicated heavy charged particles were more effective than x-rays for inducing morphological changes; however there were no qualitative differences in damage produced by heavy charged particles and x-rays. Characteristic changes after irradiation included abnormal bow patterns, posterior and anterior migration of nucleated cells in the cortex, swelling of fibers and the development of swirls of epithelium at the anterior pole. The results also indicated that the degree of degenerative changes in lens fibers increases with increasing radiation dose and sampling time. The radiation-induced injury to lens fibers also showed a relationship to linear energy transfer (LET). The qualitative observations at 24 months indicated that low energy 40Ar (600 KeV/micron) is less effective than high energy 40Ar particles (100 KeV/micron)1 and radiation-induced injury in the lens fibers shows an LET-dependence when the ionizing density is less than 100 KeV/micron. At 30 months after heavy charged particle irradiation, the changes in control lens were the swollen fibers, while in the 40Ar-irradiated animals, aberrant fibers with abnormal nuclei, amorphous materials and debris were observed.

Animals↗

PubMed1986

Evidence for reduced capacity for damage accumulation and repair in plateau-phase C3H 10T1/2 cells following multiple-dose irradiation with gamma rays.

The effects of multiple-dose gamma irradiation on the shape of survival curves were studied with mouse C3H 10T1/2 cells maintained in contact-inhibited plateau phase. The dose-fractionation intervals included 3, 6, and 24 h. Following three fractionated doses (5 Gy per dose) of exposures, cells responded to further irradiation by displaying a survival curve with a much reduced shoulder width (Dq) compared to that of the survival curve measured in cells irradiated with single-graded doses alone. The effect on the mean lethal dose (D0) was small and appeared to be significant. The effect on reduction of Dq could not be completely overcome by lengthening the fractionation intervals from 3 to 6 h or 24 h, times in which repair of sublethal damage (SLD) measured by simple split-dose scheme and potentially lethal damage (PLD) measured by postirradiation incubation was completed. Other experiments showed that pretreatments of cells with fractionated irradiation appeared to slow down the cellular repair processes of SLD and PLD. Therefore, the observed change in the shape of survival curves after fractionation treatments may be attributed to a reduction of the cells' capacity for damage accumulation by an enhancement of the lethal expression of SLD and PLD. Although the molecular mechanism(s) is not known, the results of this study indicate that the acute graded dose-survival curve cannot be used a priori to extrapolate and reliably predict results of hyperfractionation. It is probable that for a nondividing or slowly dividing cell population, such an extrapolation may lead to an underestimation of cell killing. Furthermore, the findings of this investigation appear to support an interpretation, alternative to the high-linear energy transfer (LET) track-end postulate, for the effects on cell survival seen at low doses or low dose rates.

Animals↗

PubMed1986

[Radiotherapy of malignant melanoma of the skin--a renaissance?].

Surgery is without question the treatment of choice for the malignant melanoma (MM) of the skin. Radiotherapy, on the other hand, has been more and more neglected, especially because of the opinion that melanomas are "radioresistant". Because there is an increasing interest in the radiotherapy of MM in the recent years, and reviewing the experimental and clinical findings in the literature the following points are made: MM is not a "radioresistant" tumour and therefore the expression reduced radiosensitivity should be used instead; radiotherapy with beams of low linear energy transfer (LET) is also possible if the techniques involve the use of high dose per fraction or multiple fractions per day; different types of MM of the skin show a variable radiosensitivity in vitro and in vivo; and indications still exist for the radiotherapy of MM. All possibilities for the use of radiotherapy alone in MM have not yet been exhausted.

Cell Survival↗

PubMed1985

Heavy-ion effects on mammalian cells: inactivation measurements with different cell lines.

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.

Animals↗

PubMed1982

Future directions in the therapy for large bowel cancer.

The essence of clinical research success is a blending of modality-oriented development and disease oriented strategy. Development therapeutics begins with single institution pilot, or exploratory, studies in which the treatment itself is more important than the strategic approach to the disease(s) being treated. Ultimately, if the exploratory studies are encouraging, the confirmatory and explanatory studies (Phase II--III) which follow will be disease oriented. Advances in the treatment of colorectal cancer will, it is hoped, come from new developmental therapeutics in chemotherapy, radiation therapy and biologic response modifier therapy. Developments in chemotherapy involve a steady stream of new drugs which are entering clinical trial from the drug development program of the NCI as well as from the pharmaceutical industry. These drugs include new structures and analogues of structures known to be active in some tumor types. In the latter category particular emphasis is being placed on new anthracycline analogues of doxorubicin and analogues of cisplatinum diammine dichloride. Recognizing the importance of colorectal cancer experimental models for this tumor are being given prominence in the prediction for now active drugs. These include transpantable rodent colon tumors and human colon tumors grown in nude mice or in a subrenal capsule system. In addition, the clonogenic assay of human tumor stem cells is under active investigation. It is hoped that this assay will be able to help predict which patients with colorectal tumors will respond to the given available drugs, and help predict the selection of new active drugs for colorectal cancer. Examples of new developments in radiation oncology which may have eventual impact on large bowel cancer include: (1) high linear energy transfer deliverence techniques such as neutrons, heavy ions and pi-mesons; (2) radiation sensitizers such as misonidazole, desmethylmisonidazole and newer electronic affinic compounds; (3) radiation protectors such as WR-2727; and (4) new fractionation schedules. In addition hyperthermia is evolving as a viable approach to killing neoplastic cells both alone and in conjunction with x-ray therapy. The biologic response modifiers (BRM) are a new and exciting development in cancer treatment. These are materials which hopefully will modify the hosts ability to react to neoplastic cells in a way which will be of therapeutic benefit either by itself or in conjunction with other therapies. Among BRMs of current interest are the interferons and thymic hormones. The interferons have demonstrated some ability to shrink clinically evident breast cancers and lymphomas and when supplies permit studies in bowel cancer will be great interest.

Antineoplastic Agents↗

PubMed1983

Is immediate chest radiotherapy obligatory for any or all patients with limited-stage non-small cell carcinoma of the lung? Yes.

External irradiation with the greatest technical sophistication available is indicated in all patients with inoperable non-small cell carcinoma of the lung confined to the primary site and to regional lymph nodes including the ipsilateral supraclavicular nodes. Irradiation with moderately high doses results in responses in 40%-65% of all patients. With irradiation to a level of at least 6000 rad in 30 fractions in 6 weeks, greater than 60% of patients never fail in the chest. Some of these patients become long-term, disease-free survivors. Until it is possible clearly to predict those patients who do not respond and thereby to justify an approach other than thoracic irradiation, it is necessary to offer radiation therapy to all of these patients. Since local control is far from satisfactory, one can certainly justify investigating new approaches, including further increases of the total dose, altered fractionation schemes, addition of radiosensitizers, and high linear energy transfer radiations. Since distant metastases frequently appear in spite of thorough pretreatment evaluations, one can also justify investigating the addition of systemic agents, both cytotoxic drugs and biologic response modifiers. Benefit from these systemic approaches may be completely masked, even in patients with disseminated disease, by failure to prevent complications and death due to the intrathoracic tumor.

Adenocarcinoma↗

PubMedDate not supplied

[Biological effectiveness of ionizing radiations of various quality in Escherichia coli bacteria (a theoretical analysis). A cell inactivation model].

The dependence of the radiosensitivity of bacteria (the wild type, superresistant and rec-mutants) on linear energy transfer (LET) is considered. A nonformal model of inactivation of different bacterial mutants has been developed on the basis of the experimental data available. The concept of "metastable siles" (MS) is introduced. MS are peculliar DNA lesions arising from the occurrence of large nucleolytic gaps on both strands of DNA. Different mechanisms responsible for MS formation are considered. The kinetic equations of the model are solved and the parameters determined for both sensitive and resistant mutants.

DNA Repair↗

PubMed1984

Interaction of heat with radiation and chemotherapy.

In using hyperthermia in the clinic, thermal dosimetry is essential and is discussed in terms of equating time-temperature relationships for an isoeffect to an equivalent time at a reference temperature, 43 degrees for example. In applying time-temperature-equivalence, the sequence between heat and radiation and between two heat treatments, radiation dose rate, linear energy transfer, and physiological parameters must be considered. Furthermore, thermal tolerance observed for both heat killing and heat radiosensitization, especially for doses of 400 rads or greater, may be considered as a thermal dose modifier. When hyperthermia is combined with drugs, most of the factors mentioned above are probably important and need careful evaluation, including the applicability of calculating equivalent time at a reference temperature. Examples are given for delayed heat sensitization after depletion of intracellular polyamines and for heat partially overcoming resistance to 1,3-bis-2-chloroethylnitrosourea in order to illustrate the importance of understanding heat effects on formation of reactive drug intermediates, permeability of drugs into cells, and damage to target molecules.

Animals↗

PubMed1983

Response of colony-forming units-spleen to heavy charged particles.

Survival of colony-forming units-spleen (CFU-S) was measured after single doses of photons or heavy charged particles from the BEVALAC. The purposes were to define the radiosensitivity to heavy ions used medically and to evaluate relationships between relative biological effectiveness (RBE) and dose-averaged linear energy transfer (LET infinity). In in vitro irradiation experiments. CFU-S suspensions were exposed to 220 kVp X rays or to 20Ne (372 MeV/micron) or 40Ar (447 MeV/micron) particles in the plateau portion of the Bragg curve. In in vivo irradiation experiments, donor mice from which CFU-S were harvested were exposed to 12C (400 MeV/micron). 20Ne (400 or 670 MeV/micron), or 40Ar (570 MeV/micron) particles in Bragg peaks spread to 4 or 10 cm by spiral ridge filters. Based on RBE at 10 survival, the maximum RBE of 2.1 was observed for 40Ar particles characterized by an LET infinity of approximately 100 keV/micron. Lower RBEs were determined at lower or higher estimated values of LET infinity and ranged from 1.1 for low energy 40Ar particles to 1.5-1.6 for low energy 12C and 20Ne. The responses of CFU-S are compared with responses of other model systems to heavy charged particles and with the reported sensitivity of CFU-S to neutrons of various energies. The maximum RBE reported here, 2.1 for high energy 40Ar particles, is somewhat lower than values reported for fission-spectrum neutrons, and is appreciably lower than values for monoenergetic 0.43-1.8 MeV neutrons. Low energy 12C and 20Ne particles have RBEs in the range of values reported for 14.7 MeV neutrons.

Animals↗

PubMed1984

Accelerated heavy particles and the lens. I. Cataractogenic potential.

The effect of varying doses of accelerated (570 MeV/ amu ) argon ions on the rat lens is described with detailed observations on the sequence of development of the cataracts, the time-dose relationship, and the analysis of their cataractogenic potential. The relative biological effectiveness (RBE) of the heavy particles for cataract production, compared to low linear energy transfer (LET) radiation (X rays), has been established. These data indicate that, as with neutrons, the RBE increases with decreasing dose and that at a dose of 0.05 Gy an RBE of about 40 was observed.

Animals↗

PubMed1984

Methodologies for predicting the expected combined stochastic radiobiological effects of different ionizing radiations and some applications.

A methodology for predicting the expected combined stochastic radiobiological effects of sequential exposure to different ionizing radiations is used to arrive at a methodology for predicting the radiobiological effects of simultaneous exposure. Both methodologies require developing additive-damage dose-effect models. Additive-damage dose-effect models are derived assuming (a) each radiation comprised by the combined exposure produces initial damage called critical damage that could lead to the radiobiological effect of interest; (b) doses of different radiations that lead to the same level of radiobiological effect (or risk) can be viewed as producing the same amount of critical damage and being indistinguishable as far as the effects of subsequently administered radiation. Derived dose-effect functions that describe the risk per individual, conditional on radiation dose, are called risk functions. The methodologies allow the use of known radiation-specific risk functions to derive risk functions for combined effects of different radiations. The risk functions for combined exposure to different radiations are called global risk functions. For sequential exposures to different ionizing radiations, the global risk functions derived depend on how individual radiation doses are ordered. Global risk functions can also differ for sequential and simultaneous exposure. The methodologies are used to account for some previously unexplained radiobiological effects of combined exposure to high and low linear-energy-transfer radiations.

Alpha Particles↗

PubMed1983

Cataract production in mice by heavy charged argon, neon, and carbon particles.

The cataractogenic potential in mice of heavy charged particles from the Bevalac was examined in relation to dose, linear energy transfer (LET), and time following exposure. BALB/c X C57/b1(6) (CB6F1) mice were exposed to graded single doses (0.05-0.9 Gy) of 570-MeV 40Ar, 425-MeV 20Ne, or 400-MeV 12C particles in the plateau portion of the Bragg curve. Lenses were examined by slit lamp biomicroscopy over a 21-month period. The cataract severity was scored subjectively on a scale of 0 to 4 and compared to the opacities induced by 225-kVp X rays. Both the onset and density of the lens opacities were related to dose, and opacification progressed throughout the entire period of observation. In terms of degree of opacification and rates of onset and progression, the cataractogenic response to 40Ar particles was greater than to either 20Ne or 12C particles. Discrimination between the effects of 20Ne and 12C was possible only at the higher doses employed (0.6 and 0.9 Gy) and only at some observation times. Based on average cataract density at the several observation times, the relative biological effectiveness (RBE) of 40Ar particles is estimated to be 3 to 5 over a cataract score range of about 1.5-3.0 (0.15-0.9 Gy). The RBE for 20Ne and 12C particles is probably somewhat greater than 1.0. The consistency of replicate lens examinations and challenges of the subjective scoring system are discussed.

Animals↗

PubMed1981

Radiation therapy for soft tissue sarcoma.

Soft tissue sarcomas can be adequately treated with wide local excision and postoperative irradiation, rather than the amputation of the affected extremity. Local control and good function can be achieved in the great majority of patients treated with radiation therapy, with particularly good results (95% local control) obtained for lesions of the distal extremity i.e., below the elbow or knee. The most common site of failure is distant metastasis, and the outstanding prognostic indicator is histologic grade. Disease-free survival correlates strongly with grade, with 85%, 51%, and 17% 2-yr disease-free survival for grades 1, 2, and 3, respectively. Lymph node metastasis is an uncommon first site of failure, and prophylactic nodal irradiation or lymphadenectomy is not recommended. The value of chemotherapy or immunotherapy is not firmly established as far as enhancing local control. It is hoped that distant metastasis can be prevented by the use of such adjuvant therapy. Locally advanced, nonresectable sarcoma may be better treated with high linear energy transfer (LET) radiation, and promising results have been reported with fast neutron treatment.

Breast Neoplasms↗

PubMedDate not supplied

[Action of protons with 25 and 50 MeV energies on the chromosomes of human peripheral blood lymphocytes in vitro].

The frequency and type of chromosomal abberations in human lymphocytes induced by 25, 50, 645 MeV protons and 200 kv x-rays were studied. It was shown that the yield of one-hit acentric fragments increased linearly and that of double-break aberrations increased exponentially with the irradiation dose. It was demonstrated that under the influence of radiations with high linear energy transfer the number of paired fragments increased and that of dicentrics and rings decreased. The test of total yield of chromosomal aberrations and their specific types helped to derive coefficients of relative biological effectiveness of the above irradiations. There was a quantitative correlation between the dose and yield of individual aberration types. This suggests that lymphocytes can be used as a biological dosimeter for dose measurement.

Cells, Cultured↗