Cancer Incidence in C3H Mice Protected from Lethal Total-Body Radiation after Amifostine

Abstract

Amifostine is a potent antioxidant that protects against ionizing radiation effects. In this study, we evaluated the effect of Amifostine administered before total-body irradiation (TBI), at a drug dose that protects against TBI lethality, for potential protection against radiation-induced late effects such as a shortened lifespan and cancer. Three groups of mice were studied: 0 Gy control; 10.8 Gy TBI with Amifostine pretreatment; and 5.4 Gy TBI alone. Animals were monitored for their entire lifespan. The median survival times for mice receiving 0, 5.4 or 10.8 Gy TBI were 706, 460 and 491 days, respectively. Median survival of both irradiated groups was significantly shorter compared to nonirradiated mice (P < 0.0001). Cancer incidence (hematopoietic and solid tumors) was similar between the irradiated groups and was significantly greater than for the 0 Gy controls. The ratio of hematopoietic-to-solid tumors differed among the groups, with the 5.4 Gy group having a higher incidence of hematopoietic neoplasms compared to the 10.8 Gy/Amifostine group (1.8-fold). Solid tumor incidence was greater in the 10.8 Gy/Amifostine group (1.6-fold). There are few mouse lifespan studies for agents that protect against radiation-induced lethality. Mice treated with 10.8 Gy/Amifostine yielded a lower incidence of hematopoietic neoplasms and higher incidence of solid neoplasms. In conclusion, mice protected from lethal TBI have a shortened lifespan, due in large part to cancer induction after exposure compared to nonexposed controls. Amifostine treatment did protect against radiation-induced hematopoietic tumors, while protection against solid neoplasms was significant but incomplete.

Neoadjuvant Radiotherapy-Related Wound Morbidity in Soft Tissue Sarcoma: Perspectives for Radioprotective Agents

“…Amifostine is an antioxidant and radioprotector that works by scavenging hydroxyl radicals (HO • ) [135]. In a phase III clinical trial of squamous head and neck cancer patients, amifostine was found to have protective effects on acute and delayed xerostomia but not severe oral mucositis [136] and has been studied broadly in clinical trials with RT with or without concurrent chemotherapy [137].…”

Therapeutic effects of Co-Venenum Bufonis Oral Liquid on radiation-induced esophagitis in rats

“…The irradiation exposure was performed by using X-Ray 225 (Radsource, North Branford, CT, USA) with exposure dose rate of 219.93 cGy/min. According to the literature [ 10 ], the total irradiation dose was 30 Gy and the irradiated area was 2 cm×5 cm and 5 mm lead was used.…”

“…Endoscopy, mucosal biopsy and esophageal barium film were used to test the pathological changes and evaluate the efficacy of drugs [17]. The changes of body weight, survival time, esophageal pathology and inflammatory cell score have also been used to evaluate the efficacy of the drug in the treatment of radiation induced esophagitis in C3H mice [10].…”

Radiation countermeasures for hematopoietic acute radiation syndrome: growth factors, cytokines and beyond

“…post-exposure growth factors and cytokines) (Seed et al 2014;Hofer et al 2017;Singh and Seed 2019). Amifostine treatment also protected against radiation-induced hematopoietic tumors, while protection against solid neoplasms was significant but incomplete (Cook et al 2018).…”