SummaryThe enhancement of oncogenic transformation in the C3H10T½ system by protraction of a high-LET irradiation has been widely reported. Prima facie, the results are inconsistent in that some but not all experiments have shown an enhancement. That the reported data follow a clear pattern is shown, and a model whose predictions are quantitatively consistent with these trends is discussed. The model, developed from that originally suggested by Rossi and Kellerer (1986), postulates that cells are especially sensitive to radiation during some period of their cycle. A sensitive period of about 1 h is shown to yield predictions consistent with all available data. If the suggested model is realistic and applicable to human cells in vivo, little enhancement would be expected for high-LET radiations such as from radon daughters or HZE cosmic rays, though an effect might be expected from trapped protons on astronauts in earth orbit. For fission neutrons a time-dependent factor of N = 2 in the formula for dose eq...

The inverse dose-rate effect for oncogenic transformation by neutrons and charged particles: a plausible interpretation consistent with published data.

The effects of exposure to high and very low fluence alpha-particles on the G1 checkpoint were investigated in human diploid fibroblasts irradiated and released from density-inhibited confluent cultures by the use of the cumulative labeling index method. Transient and permanent arrests in G1 occurred in fibroblast populations exposed to mean doses as low as 1 cGy, suggesting that nontraversed bystander cells may contribute to the low dose response. In cells exposed to high fluences, the G1 checkpoint is at least as extensive as in gamma-irradiated cells. In contrast to gamma-irradiated cells, neither repair of potentially lethal damage nor a reduction in the fraction of cells transiently or permanently arrested in G1 were observed in cells held in confluence for 6 h after alpha-particle irradiation. Studies with isogenic wild-type, p53-/-, and p21Waf1-/- mouse embryo fibroblasts exposed to either gamma or alpha-particle radiation revealed a total lack of G1 arrest in either p53-/- or p21waf1-/- cells, indicating that the G1 checkpoint in wild-type cells is p53-dependent and that p21Wf1 fully mediates the role of p53 in its induction. In contrast to human cells, mouse embryo fibroblasts do not undergo a permanent G1 arrest. Except under conditions favoring potentially lethal damage repair, a comparable expression pattern of p53, p21Waf1, and other cell cycle-regulated proteins (pRb, p34cdc2, and cyclin B1) was observed in alpha-particle or gamma-irradiated human fibroblasts.

https://cancerres.aacrjournals.org/content/canres/60/10/2623.full.pdf

High and Low Fluences of α-Particles Induce a G1 Checkpoint in Human Diploid Fibroblasts

Some recent epidemiological studies have shown a positive association between cancer incidence and exposure to electromagnetic (EM) fields. Evidence from in vitro studies indicates that this effect could be due to synergistic interaction between EM fields and tumor promoters. However, no dose-response data related directly to carcinogenesis have been published. In this study, actively growing cultures of C3H/10T 1/2 cells were exposed for 24 h to 2.45-GHz microwaves pulse-modulated at 120 Hz. Conditions of EM-field exposure were designed to simulate low-field exposures (specific absorption rate 0.1, 1, or 4.4 W/kg; the corresponding peak amplitudes were electric field 18, 56, or 120 V/m, magnetic field 0.09, 0.27, or 0.56 μT, respectively). In separate experiments, a 24-h EM-field exposure at 4.4 W/kg was preceded or followed by X irradiation at 0.5, 1, or 1.5 Gy. Cells were assayed for cell survival and neoplastic transformation with or without post-treatment administration of 0.1 μg/ml of 12-O-tetradeca...

Neoplastic Transformation of C3H/10T 1/2 Cells Following Exposure to 120-Hz Modulated 2.45-GHz Microwaves and Phorbol Ester Tumor Promoter

SummaryA versatile irradiator has been constructed for in vitro irradiation of mammalian cells with α-particles of well-defined energy, LET, direction, dose and dose rate. It is based on ∼ 1·2 × 109 Bq of 238Pu (on a platinum disc) contained in a He-filled chamber. In a standard configuration, monolayers of cells grown in 10 Hostaphan-based dishes are irradiated with 3·26 ± 0·22 MeV α-particles (LET 121 keV μm−1) at selectable dose rates from ∼ 2 Gy min−1 down to < 10−4 Gy min−1 (i.e. fluence rates of 1 × 107 cm−2 min−1 to 3 × 102 cm−2 min−1). Single dishes can be irradiated at dose rates up to 24 Gy min−1 (fluence rate 1 × 108 cm−2 min−1). Incident energy and LET can be varied from 0·8 to 4·2 MeV and 266 to 102 keV μm−1, respectively. The irradiator has full incubation and gassing facilities for protracted irradiations. The irradiator is particularly suitable for in vitro analytical studies of the biological effects of α-particles of energies and LETs similar to those which cells may receive in vivo from...

A versatile plutonium-238 irradiator for radiobiological studies with alpha-particles.

The latest theories and results on the early effects of radiation on DNA are presented and summarized in this text. Contributions are made by leading radiation physicists, chemists and biologists. All three subject areas have shown great advances in recent years, for example, the computer codes and Monte Carlo calculations used by physicists, the deeper understanding of free radical intermediates by chemists, and the techniques of molecular biology. The reader will gain an insight into the different scientific languages and approaches used by physicists, chemists and biologists in the understanding of the effects of radiation on living matter. This book of proceedings on radiation biology, radiation chemistry and radiation physics is intended for researchers and advanced students.

The Early Effects of Radiation on DNA

The findings of Hill et al. (1984) on the greatly enhanced transformation frequencies at very low dose rates of fission neutrons induced us to perform an analogous study with alpha-particles at comparable dose rates. Transformation frequencies were determined with gamma-rays at high dose rate (0.5 Gy/min), and with alpha-particles at high (0.2 Gy/min) and at low dose rates (0.83-2.5 mGy/min) in the C3H 10T1/2 cell system. alpha-particles were substantially more effective than gamma-rays, both for cell inactivation and for neoplastic transformation at high and low dose rates. The relative biological effectiveness (RBE) for cell inactivation and for neoplastic transformation was of similar magnitude, and ranged from about 3 at an alpha-particle dose of 2 Gy to values of the order of 10 at 0.25 Gy. In contrast to the experiments of Hill et al. (1984) with fission neutrons, no increased transformation frequencies were observed when the alpha-particle dose was protracted over several hours.

/pdf/absence-of-a-dose-rate-effect-in-the-transformation-of-c3h-2kobnm8y2y.pdf

Absence of A Dose-rate Effect in the Transformation of C3H 10T1/2 Cells by α-particles

Deep learning-based radiological image analysis could facilitate use of chest x-rays as a triaging tool for COVID-19 diagnosis in resource-limited settings. This study sought to determine whether a modified commercially available deep learning algorithm (M-qXR) could risk stratify patients with suspected COVID-19 infections.A dual track clinical validation study was designed to assess the clinical accuracy of M-qXR. The algorithm evaluated all Chest-X-rays (CXRs) performed during the study period for abnormal findings and assigned a COVID-19 risk score. Four independent radiologists served as radiological ground truth. The M-qXR algorithm output was compared against radiological ground truth and summary statistics for prediction accuracy were calculated. In addition, patients who underwent both PCR testing and CXR for suspected COVID-19 infection were included in a co-occurrence matrix to assess the sensitivity and specificity of the M-qXR algorithm.625 CXRs were included in the clinical validation study. 98% of total interpretations made by M-qXR agreed with ground truth (p = 0.25). M-qXR correctly identified the presence or absence of pulmonary opacities in 94% of CXR interpretations. M-qXR's sensitivity, specificity, PPV, and NPV for detecting pulmonary opacities were 94%, 95%, 99%, and 88% respectively. M-qXR correctly identified the presence or absence of pulmonary consolidation in 88% of CXR interpretations (p = 0.48). M-qXR's sensitivity, specificity, PPV, and NPV for detecting pulmonary consolidation were 91%, 84%, 89%, and 86% respectively. Furthermore, 113 PCR-confirmed COVID-19 cases were used to create a co-occurrence matrix between M-qXR's COVID-19 risk score and COVID-19 PCR test results. The PPV and NPV of a medium to high COVID-19 risk score assigned by M-qXR yielding a positive COVID-19 PCR test result was estimated to be 89.7% and 80.4% respectively.M-qXR was found to have comparable accuracy to radiological ground truth in detecting radiographic abnormalities on CXR suggestive of COVID-19. 

https://doi.org/10.1016/j.ibmed.2022.100049

Using artificial intelligence to risk stratify COVID-19 patients based on chest X-ray findings

Intrathoracic Spindle Cell Lipoma Causing Thoracic Outlet Syndrome

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Absence of A Dose-rate Effect in the Transformation of C3H 10T1/2 Cells by α-particles

Using artificial intelligence to risk stratify COVID-19 patients based on chest X-ray findings

Intrathoracic Spindle Cell Lipoma Causing Thoracic Outlet Syndrome