TY - JOUR
T1 - Orthovoltage X-Rays Exhibit Increased Efficacy Compared with g-Rays in Preclinical Irradiation
AU - Bell, Brett I.
AU - Vercellino, Justin
AU - Brodin, N. Patrik
AU - Velten, Christian
AU - Nanduri, Lalitha S.Y.
AU - Nagesh, Prashanth K.B.
AU - Tanaka, Kathryn E.
AU - Fang, Yanan
AU - Wang, Yanhua
AU - MacEdo, Rodney
AU - English, Jeb
AU - Schumacher, Michelle M.
AU - Duddempudi, Phaneendra K.
AU - Asp, Patrik
AU - Koba, Wade
AU - Shajahan, Shahin
AU - Liu, Laibin
AU - Tome, Wolfgang A.
AU - Yang, Weng Lang
AU - Kolesnick, Richard
AU - Guha, Chandan
N1 - Funding Information:
This work was supported by R01CA257509, R01CA226861, R01CA198095, U01DK103155, U01AI138324, U01AI133608, U01AI133598, and R01AG057429. The authors thank the Albert Einstein Cancer Center for their support (P30CA013330). They also thank the Albert Einstein College of Medicine Histology and Comparative Pathology Facility, Flow Cytometry Core Facility (1S10OD026833), and Analytical Imaging Facility (1S10OD019961) for their valuable assistance with this project.
Funding Information:
J. Vercellino reports grants from NIH during the conduct of the study. L.S.Y. Nanduri reports grants from NIH during the conduct of the study. K.E. Tanaka reports grants from NIH during the conduct of the study. R. Macedo reports grants from NIH during the conduct of the study. P.K. Duddempudi reports grants from Albert Einstein College of Medicine during the conduct of the study. W. Koba reports grants from NIH during the conduct of the study. S. Shajahan reports grants from NIH during the conduct of the study. R. Kolesnick reports patents unrelated to this work (US7195775B1, US7850984B2, US10052387B2, US8562993B2, US9592238B2, US20150216971A1, US20170335014A1, US20170333413A1, US20180015183A1, US10414533B2, US10450385B2) and is a co-founder of Ceramedix Holding LLC. C. Guha reports grants from NIH during the conduct of the study; grants and personal fees from Janssen; grants from Celldex; and grants and personal fees from Varian outside the submitted work. No disclosures were reported by the other authors.
Publisher Copyright:
© 2022 American Association for Cancer Research Inc.. All rights reserved.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-22-0656
DO - 10.1158/0008-5472.CAN-22-0656
M3 - Article
C2 - 35919990
AN - SCOPUS:85135431239
SN - 0008-5472
VL - 82
SP - 2678
EP - 2691
JO - Cancer research
JF - Cancer research
IS - 15
ER -
