Evaluation of isoeffect formulae for predicting radiation-induced lung damage

Newcomb, C.; Dyk, Jake Van; Hill, Richard P.

doi:10.1016/0167-8140(93)90026-5

Cited by 47 publications

(17 citation statements)

References 18 publications

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“…The LD50/180 in animal models varies with species and strain but generally falls between 10.0 Gy and 14.0 Gy for single acute doses of ionizing radiation (Liao et al 1995; Down and Steel 1983; Franko 2010; Newcomb et al 1993). Although the threshold for pneumonitis in man is approximately 8.0 Gy, the lethal dose is approximately 10.0 Gy (Marks et al 2003; Van Dyk et al 1981).…”

Section: Discussionmentioning

confidence: 99%

The Prolonged Gastrointestinal Syndrome in Rhesus Macaques

MacVittie¹,

Bennett²,

Booth³

et al. 2012

Health Physics

108

126

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The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min−1 to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for efficacy and interaction during the concomitant evolution of acute and delayed key organ-specific subsyndromes.

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Section: Discussionmentioning

confidence: 99%

The Prolonged Gastrointestinal Syndrome in Rhesus Macaques

MacVittie¹,

Bennett²,

Booth³

et al. 2012

Health Physics

108

126

View full text Add to dashboard Cite

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“…A dose of 18 Gy (dose rate approximately 0.5 Gy/min) was given to all animals, which were irradiated in groups of four. It was anticipated from previous studies (23, 28, 29) that, at the dose rate used, this dose of 18 Gy would be approximately equivalent to 14 Gy at a dose rate above 1 Gy/min.…”

Section: Methodsmentioning

confidence: 97%

Genistein Can Mitigate the Effect of Radiation on Rat Lung Tissue

et al. 2010

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We investigated whether genistein could protect the lung from radiation-induced injury. We hypothesized that genistein would reduce the levels of inflammatory cytokines and ROS after irradiation and therefore lead to reduced DNA damage and functional deficits. Whole lungs of Sprague-Dawley rats were irradiated with 18 Gy at ~0.5 Gy/min. At 28 weeks a micronucleus assay was used to examine DNA damage and, using immunohistochemical analysis, expression of IL-1α, IL-1β, IL-6, TNF-α and TGF-β, macrophage activation, oxidative stress (8-OHdG) and collagen levels were measured. A TBARS assay was used to measure the level of malondialdehyde. Functional damage was assessed by measuring the breathing rate of the rats over the course of the experiment. The increase in breathing rate after irradiation was damped in rats receiving genistein during the phase of pneumonitis (6–10 weeks), and there was a 50–80-day delay in lethality in this group. Genistein treatment also decreased the levels of the inflammatory cytokines TNF-α, IL-1β and TGF-β and led to a reduction in collagen content, a reduction in 8-OHdG levels, and complete protection against DNA damage measured in surviving rats at 28 weeks after irradiation. These results demonstrates that genistein treatment can provide partial protection against the early (pneumonitis) effects of lung irradiation and reduce the extent of fibrosis, although not sufficiently to prevent lethality at the radiation dose used in this study.

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“…For inhomogeneous dose distributions, the dose per fraction differs greatly for different regions of the lungs. To take this dose/fraction effect into account, the physical dose distribution was converted into the normalized total dose distribution (21), using the linear-quadratic model with an ␣/␤ ratio of 3 Gy (22). The normalized total dose is defined as the total biologic equivalent dose given in fractions of 2 Gy (23).…”

Section: Dose Calculationmentioning

confidence: 99%