Non-targeted effects and the dose response for heavy ion tumor induction

Cucinotta, Francis A.; Chappell, Lori J.

doi:10.1016/j.mrfmmm.2010.01.012

Cited by 68 publications

(64 citation statements)

References 25 publications

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“…Several recent reviews have noted the importance of NTEs for high LET radiation. The supra-linear dose responses produced by NTEs at low dose can substantially increase RBE estimates and skew PDFs for cancer risk estimates (Cucinotta et al, 2013a;Barcellos-Hoff and Nyugen, 2009;Kadhim et al, 2013;Cucinotta and Chappell, 2010). Calculations for the mixed-field GCR environment are under development, however, our earlier calculations for single particle species show significant skewness in PDFs for REID predictions will occur if NTEs are modeled in conjunction with the nominal linear dose response model used for HZE particles (Cucinotta et al, 2013a).…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…We shall adopt the IDER and parameters used by Cucinotta and colleagues (6,17,39) in an analysis of murine HG tumorigenesis. They consider the data set as a whole, rather than analyzing each ion type separately, include analyses of parameter uncertainties and use information criteria to select optimal models.…”

Section: Harderian Gland Tumorigenesismentioning

confidence: 99%

“…The single-ion experiments that led to the IDER we used have, despite the discrepancies mentioned above, been influential in notions about astronaut risk (39). Corresponding mixture experiments potentially play an analogous role.…”

Section: Advantages and Disadvantages Of Synergy Analysismentioning

confidence: 99%

High-Energy Particle-Induced Tumorigenesis Throughout the Gastrointestinal Tract

et al. 2014

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“…These stresses may induce events that alter the cellular redox environment, thereby affecting the response to HZE particles. Recently, the contribution of oxidative stress generated by the nontargeted pathway to the overall responses of cell populations exposed to low fluences of HZE particles has received much attention (64,133).…”

Section: Oxygen Effectsmentioning

confidence: 99%

“…Interestingly, a dose-response model that takes into account bystander effects provided an improved fit compared to the targeted effect model in analyses of Harderian gland tumors induced in mice exposed to heavy ions (64). These data probably represent the most comprehensive study for tumor induction by heavy ions.…”

mentioning

confidence: 99%