Incidence of Acute Myeloid Leukemia and Hepatocellular Carcinoma in Mice Irradiated with 1 GeV/nucleon<sup>56</sup>Fe Ions

Weil, Michael M.; Bedford, Joel S.; Bielefeldt‐Ohmann, Helle; Ray, F. Andrew; Genik, Paula C.; Ehrhart, E. J.; Fallgren, Christina M.; Hailu, Fitsum; Battaglia, Christine L. R.; Charles, Brad; Callan, Matthew A.; Ullrich, Robert L.

doi:10.1667/rr1648.1

Cited by 109 publications

(101 citation statements)

References 30 publications

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“…Proton is ~ 50%, helium is ~25% and HZE particles with high-LET is ~25% of a given GCR simulation dose. Combining such information with previously published data that showed high-versus low-LET radiation induced a higher incidence of tumorigenesis in different mouse models (Fry et al, 1983;Trani et al, 2014;Ullrich et al, 1987;Wang et al, 2015;Weil et al, 2009), and the real risk of space radiation-induced tumorigenesis might be lower than previously estimated since high-LET radiation takes ~1/4 of total space radiation. Such a prediction needs further experiments to verify.…”

Section: Accepted Manuscriptsupporting

confidence: 61%

“…However, due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the risk of lung carcinogenesis is for astronauts following exposure to space radiation (Durante and Cucinotta, 2008), and evaluating the space radiation risk depends primarily on animal experiments. Previously, different groups using different mouse models demonstrated that high-LET radiation versus low-LET radiation has a higher risk of generating tumorigenesis in the Harderian gland (Fry et al, 1983), lung (Ullrich et al, 1987), mammary (Ullrich et al, 1987), liver (Weil et al, 2009) and colon (Trani et al, 2014). These data provide valuable information for estimating the risk of space radiation with high-LET HZE particle-induced tumorigenesis.…”

Section: Introductionmentioning

confidence: 95%

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Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

Wang

Zhang

Wang

et al. 2016

Life Sciences in Space Research

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Section: Accepted Manuscriptsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 95%

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

Wang

Zhang

Wang

et al. 2016

Life Sciences in Space Research

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“…Several reports (Fry et al, 1985;Alpen et al, 1993;Dicello et al, 2004;Weil et al, 2009Weil et al, , 2014Grahn et al, 1992;Imaoka et al, 2007;Trani et al, 2010;Datta et al, 2013;Illa-Bochaca et al, 2014;Wang et al, 2015) have suggested that HZE particles and neutrons could produce more lethal tumors compared to tumors produced by low LET radiation or background tumors, which is a qualitative difference not accounted for in current risk estimates. Table 3 summarizes these findings from animal studies with HZE particle beams.…”

Section: Tumor Modelmentioning

confidence: 96%

Safe days in space with acceptable uncertainty from space radiation exposure

Cucinotta

Alp

Rowedder

et al. 2015

Life Sciences in Space Research

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The prediction of the risks of cancer and other late effects from space radiation exposure carries large uncertainties mostly due to the lack of information on the risks from high charge and energy (HZE) particles and other high linear energy transfer (LET) radiation. In our recent work new methods were used to consider NASA's requirement to protect against the acceptable risk of no more than 3% probability of cancer fatality estimated at the 95% confidence level. Because it is not possible that a zero-level of uncertainty could be achieved, we suggest that an acceptable uncertainty level should be defined in relationship to a probability distribution function (PDF) that only suffers from modest skewness with higher uncertainty allowed for a normal PDF. In this paper, we evaluate PDFs and the number or "safe days" in space, which are defined as the mission length where risk limits are not exceeded, for several mission scenarios at different acceptable levels of uncertainty. In addition, we briefly discuss several important issues in risk assessment including non-cancer effects, the distinct tumor spectra and lethality found in animal experiments for HZE particles compared to background or low LET radiation associated tumors, and the possibility of non-targeted effects (NTE) modifying low dose responses and increasing relative biological effectiveness (RBE) factors for tumor induction. Each of these issues skew uncertainty distributions to higher fatality probabilities with the potential to increase central values of risk estimates in the future. Therefore they will require significant research efforts to support space exploration within acceptable levels of risk and uncertainty.

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“…For instance, recent work at the Brookhaven National Laboratory accelerator has shown that the RBE of 1 GeV n 21 Fe-ions for cancer induction in mice is about 1 for leukaemia and about 20 for hepatocellular carcinoma. 119 How can the RBE be so different? The reason is most likely because of the different nature of liquid and solid cancers.…”

Section: Late Effectsmentioning

confidence: 99%

New challenges in high-energy particle radiobiology

Durante

2014

BJR

123

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Densely ionizing radiation has always been a main topic in radiobiology. In fact, a-particles and neutrons are sources of radiation exposure for the general population and workers in nuclear power plants. More recently, high-energy protons and heavy ions attracted a large interest for two applications: hadrontherapy in oncology and space radiation protection in manned space missions. For many years, studies concentrated on measurements of the relative biological effectiveness (RBE) of the energetic particles for different end points, especially cell killing (for radiotherapy) and carcinogenesis (for late effects). Although more recently, it has been shown that densely ionizing radiation elicits signalling pathways quite distinct from those involved in the cell and tissue response to photons. The response of the microenvironment to charged particles is therefore under scrutiny, and both the damage in the target and non-target tissues are relevant. The role of individual susceptibility in therapy and risk is obviously a major topic in radiation research in general, and for ion radiobiology as well. Particle radiobiology is therefore now entering into a new phase, where beyond RBE, the tissue response is considered. These results may open new applications for both cancer therapy and protection in deep space.Biological effects of densely ionizing radiation have been studied since the beginning of radiobiology. As a matter of fact, a-particles deliver the main contribution to the background radiation dose on Earth, owing to inhalation of the indoor radon.1 Neutrons have also been extensively studied because of protection of workers in nuclear power plants; use of fast neutrons in radiotherapy; and of the exposure of the survivors of the atomic bomb in Hiroshima and Nagasaki, where a neutron component was added to g-rays. Bacq and Alexander 2 already elegantly described the radiobiology of a-particles and neutrons in their 1955 seminal book.More recently, radiobiology research has focused on highenergy protons and heavy ions, mostly for two reasons: charged particle therapy (CPT) in oncology and radiation protection in manned space missions. In both cases, charged particles at energies .100 MeV n 21 are involved. The characteristic depth-dose distribution with the sharp Bragg peak at the end of the range can be exploited for killing tumours; on the other hand, densely ionizing radiation can effectively delay tissue morbidity. Notwithstanding the many differences in exposure conditions, CPT and space radiation protection share several research topics, including individual sensitivity, non-targeted effects, late stochastic effects and so forth.3 Research in these fields requires large high-energy accelerators and is often performed by the same research groups with a common interest in particle radiobiology. Research is rapidly moving forward owing to the diffusion of CPT centres in the USA, Europe, and Asia 4 and to the growing interest in manned space exploration, now a priority for all space agencies, 5 but wi...

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Incidence of Acute Myeloid Leukemia and Hepatocellular Carcinoma in Mice Irradiated with 1 GeV/nucleon⁵⁶Fe Ions

Cited by 109 publications

References 30 publications

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

Safe days in space with acceptable uncertainty from space radiation exposure

New challenges in high-energy particle radiobiology

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Incidence of Acute Myeloid Leukemia and Hepatocellular Carcinoma in Mice Irradiated with 1 GeV/nucleon56Fe Ions

Cited by 109 publications

References 30 publications

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

Safe days in space with acceptable uncertainty from space radiation exposure

New challenges in high-energy particle radiobiology

Contact Info

Product

Resources

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Incidence of Acute Myeloid Leukemia and Hepatocellular Carcinoma in Mice Irradiated with 1 GeV/nucleon⁵⁶Fe Ions