A Comparative Dose-response Relationship Between Sexes for Mortality and Morbidity of Radiation-induced Lung Injury in the Rhesus Macaque
Autor: | M.K. Jackson, William E. Jackson, Thomas J. MacVittie, Ann M. Farese, Karla D. Thrall, Saikanth Mahendra |
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Rok vydání: | 2019 |
Předmět: |
Male
Oncology medicine.medical_specialty Epidemiology Health Toxicology and Mutagenesis Lung injury Macaque 030218 nuclear medicine & medical imaging 03 medical and health sciences Sex Factors 0302 clinical medicine biology.animal Internal medicine Animals Medicine Radiology Nuclear Medicine and imaging Radiation treatment planning Lung biology business.industry Dose-Response Relationship Radiation Sequela Lung Injury medicine.disease biology.organism_classification Macaca mulatta Radiation Injuries Experimental Dose–response relationship Rhesus macaque medicine.anatomical_structure Radiation-induced lung injury 030220 oncology & carcinogenesis Female Tomography X-Ray Computed business |
Zdroj: | Health Physics. 116:354-365 |
ISSN: | 1538-5159 0017-9078 |
Popis: | Radiation-induced lung injury is a characteristic, dose- and time-dependent sequela of potentially lethal, delayed effects of acute radiation exposure. Understanding of these delayed effects to include development of medical countermeasures requires well-characterized and validated animal models that mimic the human response to acute radiation and adhere to the criteria of the US Food and Drug Administration Animal Rule. The objective herein was to establish a nonhuman primate model of whole-thorax lung irradiation in female rhesus macaques. Definition of the dose-response relationship to include key signs of morbidity and mortality in the female macaque served to independently validate the recent model performed with male macaques and importantly, to establish the lack of sex and institutional bias across the dose-response relationship for radiation-induced lung injury. The study design was similar to that described previously, with the exception that female rhesus macaques were utilized. In brief, a computed tomography scan was conducted prior to irradiation and used for treatment planning. Animals in 5 cohorts (n = 8 per cohort) were exposed to a single 6-MV photon exposure focused on the lung as determined by the computed tomography scan and treatment planning at a dose of 9.5, 10, 10.5, 11, or 11.5 Gy. Subject-based supportive care, including administration of dexamethasone, was based on trigger-to-treat criteria. Clearly defined euthanasia criteria were used to determine a moribund condition over the 180-day study duration post-whole-thorax lung irradiation. Percent mortality per radiation dose was 12.5% at 9.5 Gy, 25% at 10 Gy, 62.5% at 10.5 Gy, 87.5% at 11 Gy, and 100% at 11.5 Gy. The resulting probit plot for the whole-thorax lung irradiation model estimated an LD50/180 of 10.28 Gy, which was not significantly different from the published estimate of 10.27 Gy for the male rhesus. The key parameters of morbidity and mortality support the conclusion that there is an absence of a sex influence on the radiation dose-response relationship for whole-thorax lung irradiation in the rhesus macaque. This work also provides a significant interlaboratory validation of the previously published model. |
Databáze: | OpenAIRE |
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