Abstract
Previously, we investigated the dose response for chromosomal aberration (CA) for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) particles, and showed that the dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Our results suggested that the simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. Nitric oxide (NO) has been reported as a candidate for intercellular signaling for NTE in many studies. In order to estimate the contribution of NTE components in induced CA, we measured CA with and without an NO scavenger in normal skin fibroblasts cells after exposure to 600 MeV/u and 1 GeV/u 56Fe ions, less than one direct particle traversal per cell nucleus. Yields of CA were significantly lower in fibroblasts exposed to the NO scavenger compared to controls, suggesting involvement of NO in cell signaling for induction of CA. Media transferred from irradiated cells induced CA in non-irradiated cells, and this effect was abrogated with NO scavengers. Our results strongly support the importance of NTE contributions in the formation of CA at low-particle fluence in fibroblasts.
Highlights
Long-duration space flight in deep space is becoming a closer reality
To test involvement of non-targeted effect (NTE) in chromosomal aberration (CA), media were taken from 0.2 Gy Fe-ion exposed culture at 1 hr after exposure and transferred to non-irradiated cells (Figures 2 and 3, Table 1)
Nitric oxide released to the medium is involved in non-targeted effects in human normal fibroblasts exposed to Fe ions
Summary
Long-duration space flight in deep space is becoming a closer reality. Radiation in deep space is the most significant health concern. Understanding the dependence of the induction of genomic instability on the linear energy transfer (LET) and the dose of the charged particles is critical in order to accurately assess the cancer risks from exposures during long-term space missions to the Moon or Mars [1,2]. Radiation quality, including increased tumor malignancy for high LET radiation, non-targeted effects (NTE), and dose-rate effects are among the largest uncertainties that affect predictions of space radiation induced cancer risk. Current cancer risk projections for cosmic ray proton and HZE particle exposures are extrapolated from high dose γ-rays derived from human epidemiology data using quality factors and the dose and dose-rate reduction effectiveness factor (DDREF), assuming a linear no-threshold dose response. Experimental data for risks at low doses of radiation are highly uncertain and biological responses to low doses, in the range received by astronauts during a space mission, may be affected by non-DNA targeted effects that could produce a non-linear response
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