Assessment of the effects of radiofrequency radiation on human colon epithelium cells.

OBJECTIVES: The aim of the study was to investigate the possible effects of radiofrequency radiation (RFR) at different frequencies for different exposure durations on caspase-dependent apoptosis pathways in human colon adenocarcinoma (HT-29). METHODS: HT-29 cells were exposed to 1800 MHz; 2100 MHz and 2600 MHz RFR for 3 h cont., 6 h int. and 6 h cont.. Cell viability measurements were performed by Trypan Blue exclusion assay and the gene expressions of CASP8, CASP9, CASP3 and CASP12 were analyzed using qRT-PCR. RESULTS: Exposure to 2100 MHz RFR for all 3 durations of exposures was more effective for the ratio of the number of viable HT-29 cells w.r.t 1800 MHz RFR and 2600 MHz RFR exposures. After 2100 MHz RFR exposure, caspase activation increased significantly (for 3h cont. and 6 h int. exposures CASP8 and CASP9 levels; for 6 h cont. exposure CASP3 levels) (p 0.05). CONCLUSION: Decreases in the cell viability of HT-29 cells for certain frequencies and also durations are consistent with significant increases in caspase activations. The results of caspase activation after 1800 MHz or 2600 MHz RFR exposures can be interpreted as the activation of different types of cell death pathway by caspase signaling cascades (Fig. 15, Ref. 56).

Development and Preliminary Evaluation of a Murine Model of Chronic Radiation-Induced Proctitis.

PURPOSE: Radiotherapy (RT) is commonly used to treat most pelvic malignancies. While treatment is often effective, curative radiation doses to the rectum can result in chronic radiation-induced proctitis, which is characterized by diarrhea, tenesmus, and/or rectal bleeding, recently termed pelvic radiation disease. An animal model of chronic radiation-induced proctitis would be useful to test both preventative and therapeutic strategies to limit this morbidity but has been elusive because of the high rodent mortality associated with acute bowel RT injury. The objective of this research was to develop a novel mouse model of chronic radiation-induced proctitis using advanced technology. METHODS AND MATERIALS: Using an X-RAD 225-Cx (Precision X-Ray) small animal irradiator, multiple plan configurations were evaluated for planning treatment volume and organ-at-risk avoidance to deliver a 15 Gy 3D conformal treatment plan. The final plan was verified by high resolution 3D dosimetry (PRESAGE/optical-CT), and delivered using a single arc. Mice were monitored for mortality for 250 days, followed by histopathological correlates including mucicarmine, Masson's trichrome, and fecal pellet length. RESULTS: Six beam arrangements were considered: single and parallel-opposed fields with whole-pelvis coverage, and collimated fields in parallel-opposed, 3-field, 4-field, and arc geometries. A collimated arc plan offered superior planning treatment volume coverage and organ-at-risk avoidance compared to whole-pelvis irradiation. Treatment verification with PRESAGE 3D dosimetry (Heuris Inc) showed >99% of voxels passing gamma analysis with 2%/2 mm criteria. Our treatment resulted in no acute mortality and 40% mortality at 250 days. Histopathological analysis showed increased mucous production and fibrosis of the irradiated colon, but no change in fecal pellet length. CONCLUSIONS: Our model was able to target successfully lower colon and rectum with lower mortality than other published models. This permitted measurement of late effects that recapitulate some features of rectal damage in humans.

Application of the ICRP/ICRU reference computational phantoms to internal dosimetry: calculation of specific absorbed fractions of energy for photons and electrons.

The emission of radiation from a contaminated body region is connected with the dose received by radiosensitive tissue through the specific absorbed fractions (SAFs) of emitted energy, which is therefore an essential quantity for internal dose assessment. A set of SAFs were calculated using the new adult reference computational phantoms, released by the International Commission on Radiological Protection (ICRP) together with the International Commission on Radiation Units and Measurements (ICRU). Part of these results has been recently published in ICRP Publication 110 (2009 Adult reference computational phantoms (Oxford: Elsevier)). In this paper, we mainly discuss the results and also present them in numeric form. The emission of monoenergetic photons and electrons with energies ranging from 10 keV to 10 MeV was simulated for three source organs: lungs, thyroid and liver. SAFs were calculated for four target regions in the body: lungs, colon wall, breasts and stomach wall. For quality assurance purposes, the simulations were performed simultaneously at the Helmholtz Zentrum München (HMGU, Germany) and at the Institute for Radiological Protection and Nuclear Safety (IRSN, France), using the Monte Carlo transport codes EGSnrc and MCNPX, respectively. The comparison of results shows overall agreement for photons and high-energy electrons with differences lower than 8%. Nevertheless, significant differences were found for electrons at lower energy for distant source/target organ pairs. Finally, the results for photons were compared to the SAF values derived using mathematical phantoms. Significant variations that can amount to 200% were found. The main reason for these differences is the change of geometry in the more realistic voxel body models. For electrons, no SAFs have been computed with the mathematical phantoms; instead, approximate formulae have been used by both the Medical Internal Radiation Dose committee (MIRD) and the ICRP due to the limitations imposed by the computing power available at this time. These approximations are mainly based on the assumption that electrons are absorbed locally in the source organ itself. When electron SAFs are calculated explicitly, discrepancies with this simplifying assumption are notable, especially at high energies and for neighboring organs where the differences can reach the same order of magnitude as for photon SAFs.

Two- and three-dimensional models for risk assessment of radiation-enhanced colorectal tumorigenesis.

Astronauts may be at an increased risk for developing colorectal cancer after a prolonged interplanetary mission given the potential for greater carcinogenic effects of radiation to the colon. In addition, with an increase in age, there is a greater incidence of premalignant colon adenomas with age. In the present study, we have compared the effects of radiation on human colon epithelial cells in two-dimensional (2D) monolayer culture, in three-dimensional (3D) culture, and in intact human colon tissue biopsies. Immortalized colon epithelial cells were irradiated at the NASA Space Radiation Laboratory (NSRL) with either 1 Gy 1 GeV/nucleon (56)Fe particles or 1 Gy 1 GeV/nucleon protons and were stained at various times to assess DNA damage and repair responses. The results show more persisting damage at 24 h with iron-particle radiation compared to protons. Similar results were seen in 3D colon epithelial cell cultures in which (56)Fe-particle-irradiated specimens show more persisting damage at 24 h than those irradiated with low-LET gamma rays. We compared these results to those obtained from human colon tissue biopsies irradiated with 1 Gy gamma rays or 1 Gy 1 GeV (56)Fe particles. Observations of radiation-induced DNA damage and repair in gamma-irradiated specimens revealed more pronounced early DNA damage responses in the epithelial cell compartment compared to the stromal cell compartment. After low-LET irradiation, the damage foci mostly disappeared at 24 h. Antibodies to more than one type of DNA repair factor display this pattern of DNA damage, and staining of nonirradiated cells with nonphosphorylated DNA-PKcs shows a predominance of epithelial staining over stromal cells. Biopsy specimens irradiated with high-LET radiations also show a pattern of predominance of the DNA damage response in the highly proliferative epithelial cell compartment. Persistent unrepaired DNA damage in colon epithelial cells and the differing repair responses between the epithelial and mesenchymal compartments in tissues may enhance tumorigenesis by both stem cell transformation and alterations in the radiation-induced permissive tissue microenvironment that may potentiate cancer progression.

Assessment of patient organ dose in CT virtual colonoscopy for bowel cancer screening.

Justification and optimisation form the basic elements for the radiological protection of individuals for medical exposures. Justification includes the assessment of patient organ doses from which radiation risks are deduced. Medical radiation exposures are justified only in the case of a sufficient net benefit. For screening examinations, such as CT virtual colonoscopy, this implies that patient organ doses should be relatively low to minimise the radiation detriment. Image quality should be sufficient to maximise the potential diagnostic benefits. The Medical Exposures Directive places special attention on medical exposures as part of health screening programmes and examinations involving high individual doses to the patient, both of which apply to CT virtual colonoscopy. Technical factors were recorded for a series of patients having virtual colonoscopy on a CT scanner. In addition, the dose-length product was assessed. Patient organ doses were deduced using a CT dose calculation program. The typical effective dose was 7.5 mSv for male patients and 10.2 mSv for female patients. The effective dose is higher for female patients, as some gender-specific organs are irradiated during virtual colonoscopy. Each patient has two series of scans resulting in doses of 15 mSv for male patients and 20 mSv for female patients.

Applicability of dose conversion coefficients of ICRP 74 to Asian adult males: Monte Carlo simulation study.

International Commission on Radiological Protection (ICRP) reported comprehensive dose conversion coefficients for adult population, which is exposed to external photon sources in the Publication 74. However, those quantities were calculated from so-called stylized (or mathematical) phantoms composed of simplified mathematical surface equations so that the discrepancy between the phantoms and real human anatomy has been investigated by several authors using Caucasian-based voxel phantoms. To address anatomical and racial limitations of the stylized phantoms, several Asian-based voxel phantoms have been developed by Korean and Japanese investigators, independently. In the current study, photon dose conversion coefficients of ICRP 74 were compared with those from a total of five Asian-based male voxel phantoms, whose body dimensions were almost identical. Those of representative radio-sensitive organs (testes, red bone marrow, colon, lungs, and stomach), and effective dose conversion coefficients were obtained for comparison. Even though organ doses for testes, colon and lungs, and effective doses from ICRP 74 agreed well with those from Asian voxel phantoms within 10%, absorbed doses for red bone marrow and stomach showed significant discrepancies up to 30% which was mainly attributed to difference of phantom description between stylized and voxel phantoms. This study showed that the ICRP 74 dosimetry data, which have been reported to be unrealistic compared to those from Caucasian-based voxel phantoms, are also not appropriate for Asian population.

Radiation absorbed doses to the walls of hollow organs.

UNLABELLED: Many radiopharmaceuticals are excreted from the body through the gastrointestinal (GI) tract. The doses to the walls of the organs involved often are very significant. As significant fractions of the administered activity pass through them, these organs may receive the highest doses in the body for many radiopharmaceuticals. The absorbed dose to these walled organs, from activity in their contents, is typically calculated as 50% of the average absorbed dose to the contents, for nonpenetrating emissions. The internal surface of the GI tract, and to a certain extent the urinary bladder, is lined with a variable thickness of mucus. In addition, the radiosensitive cell populations (crypt or stem cells) are located at some depth into the mucosa. These two factors suggest that the surface dose, often used to characterize the clinically relevant absorbed doses for walled organs, may represent an overestimate in some cases. METHODS: In this study, the radiation transport code MCNP was used to simulate the deposition of energy from nonpenetrating emissions of several radionuclides of interest: 90Y, 99mTc,123I and 131I. Absorbed doses as a function of distance from the wall-contents interface were calculated for three geometric shapes representing different organs along the routes of excretion. RESULTS: The absorbed dose from nonpenetrating emissions to the sensitive cell populations was consistently lower than estimated by the standard model assumption. The simulated absorbed doses to radiosensitive cells in the GI tract for 99mTc and 123I are tenfold lower; those for 131I are fivefold lower and those for 90Y are 20% lower. CONCLUSION: This study demonstrates that the normally reported dose to the walls of hollow organs probably should be modified to account for the attenuation of these nonpenetrating emissions in the linings of the walls. This study also demonstrates that Monte Carlo codes continue to be useful in the evaluation of the dose to sensitive cells in walled organs.

Patient dose due to colon examination: dose assessment and results from a survey in The Netherlands.

PURPOSE: To determine the effective dose to the patient during radiographic colon examination. MATERIALS AND METHODS: The integral dose-area product was measured during colon examination in 1,733 patients aged 18-94 years. The effective dose was estimated from the dose-area product through computer simulations of radiation transport in anthropomorphic phantoms. The relation between patient dose and imaging or radiographic technique was considered. Patient dose from a biphasic colon examination was compared to that from a double-contrast examination. RESULTS: The factors for converting dose-area product to effective dose were 0.29 mSv x Gy(-1) x cm(-2) and 0.27 mSv x Gy(-1) x cm(-2) for the biphasic and the double-contrast studies, respectively. The average dose-area product for the biphasic colon examination was 21 Gy x cm2, of which 13 Gy x cm2 was attributed to the double-contrast views. The average dose-area product was 29 Gy x cm2 (range, 18-53 Gy x cm2); the average effective dose was 4.7 mSv (range, 2.7-8.4 mSv). CONCLUSION: Careful selection of the radiologic technique resulted in a surprisingly low dose during the biphasic colon examination. It is recommended that additional filtration of at least 0.1-mm copper be applied and that a screen-film combination with a speed class of at least 400 be used. Dose reduction when using digital techniques is often not realized in clinical practice.

Ex vivo optical properties of human colon tissue.

Using a spectrophotometer equipped with an internal integrating sphere, the absorption (mu a) and the reduced scattering (microseconds') coefficients of ex vivo human colon tissues were evaluated from reflectance and transmittance measurements. Mu a and microseconds' varied from 47.7 to 1.0 cm-1 and from 14.2 to 6.2 cm-1, respectively, on passing from 300 nm to 800 nm. These results can be used to estimate the optical penetration depths when photodynamic therapy or light-induced fluorescence procedures are used.