Effects of<sup>28</sup>Si ions, <sup>56</sup>Fe ions, and protons on the induction of murine acute myeloid leukemia and hepatocellular carcinoma

Michael M. Weil, F. Andrew Ray, Paula C. Genik, Yongjia Yu, Maureen McCarthy, Christina M. Fallgren, Robert L. Ullrich

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n <sup>28</sup>Si or 600 MeV/n <sup>56</sup>Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n <sup>28</sup>Si ions, 600 MeV/n <sup>56</sup>Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with <sup>137</sup>Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that <sup>28</sup>Si or <sup>56</sup>Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, <sup>28</sup>Si or <sup>56</sup>Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the <sup>28</sup>Si and <sup>56</sup>Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members.

Original languageEnglish (US)
Article numbere104819
JournalPLoS One
Volume9
Issue number8
DOIs
StatePublished - Aug 15 2014

Fingerprint

myeloid leukemia
hepatoma
Acute Myeloid Leukemia
protons
Protons
Hepatocellular Carcinoma
Ions
ions
Gamma Rays
mice
Gamma rays
gamma radiation
Solar Activity
Radiation
space flight
Space Flight
Space flight
United States National Aeronautics and Space Administration
neoplasms
Inbred C3H Mouse

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Effects of<sup>28</sup>Si ions, <sup>56</sup>Fe ions, and protons on the induction of murine acute myeloid leukemia and hepatocellular carcinoma. / Weil, Michael M.; Ray, F. Andrew; Genik, Paula C.; Yu, Yongjia; McCarthy, Maureen; Fallgren, Christina M.; Ullrich, Robert L.

In: PLoS One, Vol. 9, No. 8, e104819, 15.08.2014.

Research output: Contribution to journalArticle

Weil, Michael M. ; Ray, F. Andrew ; Genik, Paula C. ; Yu, Yongjia ; McCarthy, Maureen ; Fallgren, Christina M. ; Ullrich, Robert L. / Effects of<sup>28</sup>Si ions, <sup>56</sup>Fe ions, and protons on the induction of murine acute myeloid leukemia and hepatocellular carcinoma. In: PLoS One. 2014 ; Vol. 9, No. 8.
@article{836d836d309d49d8a4d28d846935a97f,
title = "Effects of28Si ions, 56Fe ions, and protons on the induction of murine acute myeloid leukemia and hepatocellular carcinoma",
abstract = "Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n 28Si or 600 MeV/n 56Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n 28Si ions, 600 MeV/n 56Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with 137Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that 28Si or 56Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, 28Si or 56Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the 28Si and 56Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members.",
author = "Weil, {Michael M.} and Ray, {F. Andrew} and Genik, {Paula C.} and Yongjia Yu and Maureen McCarthy and Fallgren, {Christina M.} and Ullrich, {Robert L.}",
year = "2014",
month = "8",
day = "15",
doi = "10.1371/journal.pone.0104819",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

TY - JOUR

T1 - Effects of28Si ions, 56Fe ions, and protons on the induction of murine acute myeloid leukemia and hepatocellular carcinoma

AU - Weil, Michael M.

AU - Ray, F. Andrew

AU - Genik, Paula C.

AU - Yu, Yongjia

AU - McCarthy, Maureen

AU - Fallgren, Christina M.

AU - Ullrich, Robert L.

PY - 2014/8/15

Y1 - 2014/8/15

N2 - Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n 28Si or 600 MeV/n 56Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n 28Si ions, 600 MeV/n 56Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with 137Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that 28Si or 56Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, 28Si or 56Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the 28Si and 56Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members.

AB - Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n 28Si or 600 MeV/n 56Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n 28Si ions, 600 MeV/n 56Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with 137Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that 28Si or 56Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, 28Si or 56Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the 28Si and 56Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members.

UR - http://www.scopus.com/inward/record.url?scp=84925672619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925672619&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0104819

DO - 10.1371/journal.pone.0104819

M3 - Article

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 8

M1 - e104819

ER -