W Shane Sills1, Janet A Tooze2, John D Olson1, David L Caudell1, Greg O Dugan1, Brendan J Johnson1, Nancy D Kock1, Rachel N Andrews3, George W Schaaf1, Richard A Lang1, J Mark Cline4. 1. Department of Pathology, Section on Comparative Medicine. 2. Department of Biostatistics and Data Sciences. 3. Department of Pathology, Section on Comparative Medicine; Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina. 4. Department of Pathology, Section on Comparative Medicine; Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina. Electronic address: jmcline@wakehealth.edu.
Abstract
PURPOSE: Cancer is a severe delayed effect of acute radiation exposure. Total-body irradiation has been associated with an increased risk of solid cancer and leukemia in Japanese atomic bomb survivors, and secondary malignancies, such as sarcoma, are a serious consequence of cancer radiation therapy. The radiation late effects cohort (RLEC) of rhesus macaques (Macaca mulatta) is a unique resource of more than 200 animals for studying the long-term consequences of total-body irradiation in an animal model that closely resembles humans at the genetic and physiologic levels. METHODS AND MATERIALS: Using clinical records, clinical imaging, histopathology, and immunohistochemistry, this retrospective study characterized the incidence of neoplasia in the RLEC. RESULTS: Since 2007, 61 neoplasms in 44 of 239 irradiated animals were documented (18.4% of the irradiated population). Only 1 neoplasm was diagnosed among the 51 nonirradiated controls of the RLEC (2.0%). The most common malignancies in the RLEC were sarcomas (38.3% of diagnoses), which are rare neoplasms in nonirradiated macaques. The most common sarcomas included malignant nerve sheath tumors and malignant glomus tumors. Carcinomas were less common (19.7% of diagnoses), and consisted primarily of renal cell and hepatocellular carcinomas. Neoplasia occurred in most major body systems, with the skin and subcutis being the most common site (40%). RNA analysis showed similarities in transcriptional profiles between RLEC and human malignant nerve sheath tumors. CONCLUSIONS: This study indicates that total-body irradiation is associated with an increased incidence of neoplasia years following irradiation, at more than double the incidence described in aging, nonirradiated animals, and promotes tumor histotypes that are rarely observed in nonirradiated, aging rhesus macaques.
PURPOSE: Cancer is a severe delayed effect of acute radiation exposure. Total-body irradiation has been associated with an increased risk of solid cancer and leukemia in Japanese atomic bomb survivors, and secondary malignancies, such as sarcoma, are a serious consequence of cancer radiation therapy. The radiation late effects cohort (RLEC) of rhesus macaques (Macaca mulatta) is a unique resource of more than 200 animals for studying the long-term consequences of total-body irradiation in an animal model that closely resembles humans at the genetic and physiologic levels. METHODS AND MATERIALS: Using clinical records, clinical imaging, histopathology, and immunohistochemistry, this retrospective study characterized the incidence of neoplasia in the RLEC. RESULTS: Since 2007, 61 neoplasms in 44 of 239 irradiated animals were documented (18.4% of the irradiated population). Only 1 neoplasm was diagnosed among the 51 nonirradiated controls of the RLEC (2.0%). The most common malignancies in the RLEC were sarcomas (38.3% of diagnoses), which are rare neoplasms in nonirradiated macaques. The most common sarcomas included malignant nerve sheath tumors and malignant glomus tumors. Carcinomas were less common (19.7% of diagnoses), and consisted primarily of renal cell and hepatocellular carcinomas. Neoplasia occurred in most major body systems, with the skin and subcutis being the most common site (40%). RNA analysis showed similarities in transcriptional profiles between RLEC and human malignant nerve sheath tumors. CONCLUSIONS: This study indicates that total-body irradiation is associated with an increased incidence of neoplasia years following irradiation, at more than double the incidence described in aging, nonirradiated animals, and promotes tumor histotypes that are rarely observed in nonirradiated, aging rhesus macaques.
Authors: Kylie Kavanagh; Michael D Dendinger; Ashley T Davis; Thomas C Register; Ryne DeBo; Greg Dugan; J Mark Cline Journal: Radiat Res Date: 2015-03-26 Impact factor: 2.841
Authors: Ann M Farese; Melanie V Cohen; Barry P Katz; Cassandra P Smith; William Jackson; Daniel M Cohen; Thomas J MacVittie Journal: Health Phys Date: 2012-10 Impact factor: 1.316
Authors: Nicole Bacarella; Alistaire Ruggiero; Ashley T Davis; Beth Uberseder; Matthew A Davis; Deanna P Bracy; David H Wasserman; J Mark Cline; Chrissy Sherrill; Kylie Kavanagh Journal: Int J Radiat Oncol Biol Phys Date: 2019-12-02 Impact factor: 7.038