Relative effectiveness at 1 gy after acute and fractionated exposures of heavy ions with different linear energy transfer for lung tumorigenesis.

Space radiation, which is comprised of high-energy charged (HZE) particles with different high-linear energy transfer (LET), induces more severe biological effects than the Earth's radiation. NASA has mandated that risk estimates of carcinogenesis induced by exposure to HZE particles with different LET be determined before conducting human explorations of Mars. Because lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in humans, it is critical the risk of that radiation-induced lung tumorigenesis be included when estimating the risks of space radiation to astronauts. To address this, we examined the incidence of lung tumorigenesis in wild-type C57BL/6 mice at 1.5 years after 1 Gy exposure (single or fractionated dose) to different types of radiation with different LET (iron, silicon, oxygen and X ray). We chose wild-type mice for this study because previous studies of radiation-induced lung tumorigenesis using mutant mice models (either downregulated tumor suppressors or upregulated oncogenes) may not accurately reflect the response of healthy individuals (astronauts) to space radiation. Our study clearly showed that HZE particles (iron, silicon and oxygen) induced a higher incidence of lung tumorigenesis than X rays, and that their relative effectiveness at 1 Gy was >6. In addition, we found that silicon exposure appears to induce more aggressive lung tumors. These results provide valuable information for future followup experiments to study the underlying mechanism of lung tumorigenesis, which will improve risk estimation of space radiation-induced lung tumorigenesis and help in the development of mitigators to reduce risk if it exceeds NASA guidelines.