Scaling Human Cancer Risks from Low LET to High LET when Dose-Effect Relationships are Complex

Area of Science:

• Space radiation biology
• Radiation carcinogenesis
• Risk assessment

Background:

• Space radiation poses significant health risks for long-duration manned missions.
• Accurate scaling of low-linear energy transfer (LET) to high-LET radiation risks is crucial for astronaut safety.
• Current methods like relative biological effectiveness (RBE) may not fully capture complex radiation effects.

Purpose of the Study:

• To introduce and evaluate a new metric, radiation effects ratio (RER), for scaling radiation risks.
• To compare RER with the standard RBE metric using experimental data.
• To assess the impact of non-targeted effects on radiation risk estimation.

Main Methods:

• Estimated RBE and RER values using heavy ion (¹²C, ²⁸Si, ⁵⁶Fe) and gamma-ray-induced intestinal tumors in a mouse model (APC^1638N/+).
• Utilized RBE and RER to calculate low-LET to high-LET risk scaling factors.
• Analyzed dose-response relationships to identify non-targeted effects.

Main Results:

• Non-targeted effects were evident at low radiation doses.
• RER was consistently lower than RBE in the presence of non-targeted effects, particularly at low doses (0.03 Gy and 0.3 Gy).
• RER values were lower than RBE by factors of 2.8-3.5 at 0.03 Gy and 1.3-1.4 at 0.3 Gy.

Conclusions:

• RER provides a more accurate method for scaling low-LET to high-LET radiation risks, especially when non-targeted effects are present.
• Using RBE for risk scaling may lead to an overestimation of low-dose, high-LET radiation cancer risks in humans.
• RER simplifies experimental designs by potentially reducing the number of radiation doses required.