WR-1065, the active metabolite of amifostine,mitigates radiation-induced delayed genomic instability |
| |
| Institution: | 1. Department of Oral Diagnosis, Area of Pathology, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo 13414-903, Brazil;2. Pathology Division, Centro Clínico de Cabeza y Cuello/Hospital Herrera Llerandi, Guatemala City 01010, Guatemala;3. Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo 13083-887, Brazil;4. Private Pathology Service, Natal, Rio Grande do Norte 59020-100, Brazil;5. Head and Neck Surgery Department, Oncology Center (CEON), Fornecedores de Cana Hospital, Piracicaba, São Paulo 13405-233, Brazil;6. Oncology Surgery Department, Cancer Center (CECAN), Santa Casa Hospital, Piracicaba, São Paulo 13419-155, Brazil;7. Institute of Pathological Anatomy, Piracicaba, São Paulo 13419-160, Brazil;1. Neurotherapeutics Lab, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India;2. Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, India;3. Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India |
| |
| Abstract: | Compounds that can protect cells from the effects of radiation are important for clinical use, in the event of an accidental or terrorist-generated radiation event, and for astronauts traveling in space. One of the major concerns regarding the use of radio-protective agents is that they may protect cells initially, but predispose surviving cells to increased genomic instability later. In this study we used WR-1065, the active metabolite of amifostine, to determine how protection from direct effects of high- and low-LET radiation exposure influences genomic stability. When added 30 min before irradiation and in high concentrations, WR-1065 protected cells from immediate radiation-induced effects as well as from delayed genomic instability. Lower, nontoxic concentrations of WR-1065 did not protect cells from death; however, it was effective in significantly decreasing delayed genomic instability in the progeny of irradiated cells. The observed increase in manganese superoxide dismutase protein levels and activity may provide an explanation for this effect. These results confirm that WR-1065 is protective against both low- and high-LET radiation-induced genomic instability in surviving cells. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
