A Monte Carlo study of macroscopic and microscopic dose descriptors for kilovoltage cellular dosimetry.

This work investigates how doses to cellular targets depend on cell morphology, as well as relations between cellular doses and doses to bulk tissues and water. Multicellular models of five healthy and cancerous soft tissues are developed based on typical values of cell compartment sizes, elemental compositions and number densities found in the literature. Cells are modelled as two concentric spheres with nucleus and cytoplasm compartments. Monte Carlo simulations are used to calculate the absorbed dose to the nucleus and cytoplasm for incident photon energies of 20-370 keV, relevant for brachytherapy, diagnostic radiology, and out-of-field radiation in higher-energy external beam radiotherapy. Simulations involving cell clusters, single cells and single nuclear cavities are carried out for cell radii between 5 and [Formula: see text]m, and nuclear radii between 2 and [Formula: see text]m. Seven nucleus and cytoplasm elemental compositions representative of animal cells are considered. The presence of a cytoplasm, extracellular matrix and surrounding cells can affect the nuclear dose by up to [Formula: see text]. Differences in cell and nucleus size can affect dose to the nucleus (cytoplasm) of the central cell in a cluster of 13 cells by up to [Formula: see text] ([Formula: see text]). Furthermore, the results of this study demonstrate that neither water nor bulk tissue are reliable substitutes for subcellular targets for incident photon energies <50 keV: nuclear (cytoplasm) doses differ from dose-to-medium by up to [Formula: see text] ([Formula: see text]), and from dose-to-water by up to [Formula: see text] ([Formula: see text]). The largest differences between dose descriptors are seen for the lowest incident photon energies; differences are less than [Formula: see text] for energies [Formula: see text]90 keV. The sensitivity of results with regard to the parameters of the microscopic tissue structure model and cell model geometry, and the importance of the nucleus and cytoplasm as targets for radiation-induced cell death emphasize the importance of accurate models for cellular dosimetry studies.

Evaluation of protective effect of propolis on parotid salivary glands in gamma-irradiated rats.

OBJECTIVE AND BACKGROUND: One of the most significant side effects of radiotherapy for head and neck cancers is xerostomia as a result of salivary gland damage. Considering pharmaco- logical effects of propolis, we evaluated its protective effect on salivary glands subjected to radiotherapy of head and neck cancer patients. MATERIALS AND METHODS: Twenty-one male albino rats (8-11 W, 190 ± 5 gm) were divided into three groups of seven animals. Scintigraphy was performed in all the groups. Then groups 1 (S) and 2 (SR) received normal saline injections and group 3 (PR) received propolis injection over 3 days. After that groups 2 and 3 were exposed to gamma radiation and all the rats underwent scintigraphic assessment on third day and 70th day after irradiation. The lips and tongues of rats in groups 2 and 3 were examined for mucositis daily in first 10 days. At the end, the parotid glands of all rats were examined histologically. RESULTS: Scintigraphy results of third and 70th day after irradiation showed statistically significant differences between PR and SR as well as SR and S. However, there was no significant difference between the PR and S groups. Histopathologic assessment demonstrated significant difference between SR, PR and S. CONCLUSION: These results suggest that propolis has protective effects on salivary gland function in animal models whilst it did not prevent radiation-induced histologic changes in tissues. Further investigations are needed to elucidate mechanisms of propolis actions. Clinical significance: Regarding to the results of this study, propolis may be useful in reduction xerostomia due to radiation to salivary glands and may be helpful for head and neck cancer patients.

Expression of heat shock proteins, Hsp70 and Hsp25, in the rat gingiva after irradiation with a CO2 laser in coagulation mode.

BACKGROUND AND OBJECTIVE: The therapeutic rationale of low-energy pulsed CO(2) laser coagulation mode has not been clarified yet. We conducted this study to characterize the effect of low-energy pulsed CO(2) laser coagulation mode irradiation of the rat gingiva in terms of the expression of heat shock proteins. MATERIAL AND METHODS: Laser irradiation was achieved with the parameters of 5 W, 600 mus pulse duration, and fluence of 326 J/cm(2). The gingiva dissected at different times after irradiation was processed for immunohistochemical examination of the expression of the heat shock proteins, Hsp70 and Hsp25. RESULTS: One hour after irradiation, the epithelial keratinocytes facing the laser wound exhibited an overexpression of Hsp70 in their nucleus. The connective tissue cells facing the laser wound, which included fibroblasts and capillary endothelial cells, showed de novo expression of Hsp70 at 3 h post-irradiation, the level of which peaked at 1 d and thereafter decreased. An enhanced and/or de novo expression of Hsp25 in the connective tissue cells facing the laser wound became evident at 3 h after irradiation, and after 1 d the Hsp25-expressing cells increased in number and spread over the wound as wound repair progressed. There was a temporospatial difference in the expression pattern between Hsp70 and Hsp25, with only a few cells appearing to co-express both heat shock proteins. CONCLUSION: The CO(2) laser treatment in coagulation mode produced the expression of heat shock proteins, and the findings suggest that while Hsp70 mainly conferred cell protection, Hsp25 was involved in the progress of wound repair as well as cell protection.

A study of the effects of phototherapy dose interval on photobiomodulation of cell cultures.

BACKGROUND AND OBJECTIVES: Dosimetry and treatment frequency are controversial phototherapy issues. Efficacy of dose fractionation on photobiomodulation was evaluated in vitro. STUDY DESIGN/MATERIALS AND METHODS: Human HEP-2 and murine L-929 cell lines were cultured in complete DMEM media. Photoradiation (670 nm, 5 J/cm2/treatment, 50 J/cm2 total energy delivery), was performed varying treatments per 24 hour period: Group I (Controls)-0, Group II-1/d, Group III-2/d, Group IV-4/d. Cell proliferation was measured using Cyquant (fluorescent DNA content) and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrasolium bromide) assays for 240 hours post therapy. A proliferation index: PI = (#Cells Experimental(t) / #Cells Control(t)) was computed. RESULTS: MTT assay results demonstrated maximal response in Group III (P < 0.05, n = 3). Cyquant maxima occurred in HEP-2 Groups II and III (P < 0.045) and L-929 Group III (P < 0.091). CONCLUSIONS: Cellular response to dose frequency varies. More frequent treatments (2/24 hours) increased metabolism and proliferation in both cell lines. Further investigation of dose fractionation in phototherapy is warranted.

The effects of single doses of beta radiation on the wound healing behaviour of human Tenon's capsule fibroblasts.

AIM: To determine the effects of single doses of beta radiation on the wound healing functions of human Tenon's capsule fibroblasts (hTf). METHODS: hTf were grown in tissue culture and irradiated with beta radiation using a strontium 90 source. The effects of beta radiation on fibroblast migration was studied using microporous transwell membranes. The effects of radiation on fibroblast contraction was investigated using a fibroblast populated collagen gels model. Production of extracellular matrix molecules (collagen I, collagen III, and fibronectin) by monolayers of irradiated fibroblasts was quantified for 14 days following single doses of beta radiation. RESULTS: Growth inhibiting doses of beta radiation did not inhibit fibroblast migration or contraction at any time point. Levels of soluble fibronectin from irradiated populations were significantly reduced after >500 cGy beta radiation. Collagen I and III levels were not reduced after any dose of radiation, and increased following treatment with 1000 cGy beta radiation. CONCLUSIONS: Growth arresting doses of beta radiation have unique effects on the wound healing behaviour of human Tenon's capsule fibroblasts. There was no significant effect on cellular migration or contraction, but ECM production was altered. Fibronectin production was inhibited following higher radiation doses, and collagen I and III production increased after 1000 cGy. The effects of single doses of beta radiation on ocular fibroblast wound healing behaviour are very different from those of 5-fluorouracil and mitomycin C, and these differences may be exploited clinically in the regulation of wound healing after glaucoma filtration surgery.

[Specific long-term cellular changes under effects of low doses of radiation]. / Osobye dolgovremennye izmeneniia kletok pri vozdeistvii radiatsii v malykh dozakh.

We examined the peculiar form of a tissue postirradiative reaction characterizing by massive, dose-independent transition of cell populations to the steady state modification with the essential raise of cell damage and cell loss probability as compared with the probability level of the same alterations in controls. We described some other signs of such type of cellular transformation. It was found that the indicated cellular condition occurred both in active and slowly proliferating tissues. The reaction occurred at relatively low doses of irradiation. Some nonmutagenic factors also may evoke such effects. Our experimental data allow us to suppose the epigenetic mechanizms taking part in the induction and preservation of such alterations. The discovered form of cellular reaction manifestating in different biological objects may be considered as some general biological tendency. The importance of the studied reaction in the pathogenesis of late consequences of low dose irradiation is discussed.

Thymic microenvironment and lymphoid responses to sublethal irradiation.

Sublethal irradiation of the murine thymus has been a useful tool for depleting the thymus of dividing immature thymocyte subsets, to sequence thymocyte differentiation events occurring from radiation-resistant precursors. This massive reduction in thymocytes also represents a model in which the bidirectional interplay between the thymic stromal cells and lymphocytes can be investigated. The purpose of this study was thus twofold: to precisely map the initiation of thymopoiesis as a prelude to assessing the effects of injected mAb to novel thymic antigens; and to use a panel of mAbs to determine the alterations in the thymic stroma during the T-cell depletion and reconstitution phases. The striking finding from this study was that following T-cell depletion, there was a marked upregulation of specific stromal antigens, which retracted with the reappearance of T cells. Thus, following sublethal irradiation, there are modifications in the thymic microenvironment that may by necessary to support renewed thymopoiesis and the complete restoration of the thymus involved the synchronous development of both the stromal and lymphocytic components.