High-LET Radiation Carcinogenesis

Fry, R.J.M.; Powers-Risius, P.; Alpen, Edward L.; Ainsworth, E. J.

doi:10.2307/3576646

Cited by 99 publications

(47 citation statements)

References 17 publications

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“…To understand the effects of high-energy, highly charged particle radiations, it is important to analyze individual end points that are surrogates for carcinogenesis in human cells, but the tumorigenic potential of these radiations in animal models must also be considered. RBE values from 27 to 40 were reported for harderian gland tumor incidence in mice exposed to 600 MeV/nucleon iron ions (60,61). Similarly, an RBE of 10 was reported for mammary tumorigenesis in female rats exposed to 1 GeV/nucleon iron ions (62).…”

Section: Discussionmentioning

confidence: 91%

Karyotypic Instability and Centrosome Aberrations in the Progeny of Finite Life-Span Human Mammary Epithelial Cells Exposed to Sparsely or Densely Ionizing Radiation

et al. 2008

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The human breast is sensitive to radiation carcinogenesis, and genomic instability occurs early in breast cancer development. This study tests the hypothesis that ionizing radiation elicits genomic instability in finite life-span human mammary epithelial cells (HMEC) and asks whether densely ionizing radiation is a more potent inducer of instability. HMEC in a non-proliferative state were exposed to X rays or 1 GeV/nucleon iron ions followed by delayed plating. Karyotypic instability and centrosome aberrations were monitored in expanded clonal isolates. Severe karyotypic instability was common in the progeny of cells that survived X-ray or iron-ion exposure. There was a lower dose threshold for severe karyotypic instability after iron-ion exposure. More than 90% of X-irradiated colonies and >60% of iron-ion-irradiated colonies showed supernumerary centrosomes at levels above the 95% upper confidence limit of the mean for unirradiated clones. A dose response was observed for centrosome aberrations for each radiation type. There was a statistically significant association between the incidence of karyotypic instability and supernumerary centrosomes for iron-ion-exposed colonies and a weaker association for X-irradiated colonies. Thus genomic instability occurs frequently in finite life-span HMEC exposed to sparsely or densely ionizing radiation and may contribute to radiation-induced breast cancer.

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Section: Discussionmentioning

confidence: 91%

Karyotypic Instability and Centrosome Aberrations in the Progeny of Finite Life-Span Human Mammary Epithelial Cells Exposed to Sparsely or Densely Ionizing Radiation

et al. 2008

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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: 91%

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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“…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 Manuscriptmentioning

confidence: 71%

“…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: 92%