Orthovoltage X-Rays Exhibit Increased Efficacy Compared with g-Rays in Preclinical Irradiation

Brett I. Bell, Justin Vercellino, N. Patrik Brodin, Christian Velten, Lalitha S.Y. Nanduri, Prashanth K.B. Nagesh, Kathryn E. Tanaka, Yanan Fang, Yanhua Wang, Rodney MacEdo, Jeb English, Michelle M. Schumacher, Phaneendra K. Duddempudi, Patrik Asp, Wade Koba, Shahin Shajahan, Laibin Liu, Wolfgang A. Tome, Weng Lang Yang, Richard KolesnickChandan Guha

Research output: Contribution to journalArticlepeer-review

Abstract

Radionuclide irradiators (137Cs and 60Co) are commonly used in preclinical studies ranging from cancer therapy to stem cell biology. Amidst concerns of radiological terrorism, there are institutional initiatives to replace radionuclide sources with lower energy X-ray sources. As researchers transition, questions remain regarding whether the biological effects of γ-rays may be recapitulated with orthovoltage X-rays because different energies may induce divergent biological effects. We therefore sought to compare the effects of orthovoltage X-rays with 1-mm Cu or Thoraeus filtration and 137Cs g-rays using mouse models of acute radiation syndrome. Following whole-body irradiation, 30-day overall survival was assessed, and the lethal dose to provoke 50% mortality within 30-days (LD50) was calculated by logistic regression. LD50 doses were 6.7 Gy, 7.4 Gy, and 8.1 Gy with 1-mm Cufiltered X-rays, Thoraeus-filtered X-rays, and 137Cs γ-rays, respectively. Comparison of bone marrow, spleen, and intestinal tissue from mice irradiated with equivalent doses indicated that injury was most severe with 1-mm Cu-filtered X-rays, which resulted in the greatest reduction in bone marrow cellularity, hematopoietic stem and progenitor populations, intestinal crypts, and OLFM4+intestinal stem cells. Thoraeus-filtered X-rays provoked an intermediate phenotype, with 137Cs showing the least damage. This study reveals a dichotomy between physical dose and biological effect as researchers transition to orthovoltage X-rays. With decreasing energy, there is increasing hematopoietic and intestinal injury, necessitating dose reduction to achieve comparable biological effects. 2022 American Association for Cancer Research.

Original languageEnglish (US)
Pages (from-to)2678-2691
Number of pages14
JournalCancer research
Volume82
Issue number15
DOIs
StatePublished - Aug 1 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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