National Aeronautical Space Administration (NASA) radiation research program is focused on enabling long duration exploration of space within acceptable risk limits. Astronauts will be exposed to radiation doses that may result in adverse long-term health risks such as damage to the nervous and cardiovascular systems and an increased risk of cancer development. During space exploration, astronauts are exposed to varying types of radiation including Galactic Cosmic Radiation (GCR) and High Atomic Number and Energy (HZE) particles. Space radiation differs from terrestrial radiation in several aspects such as ionizing pattern and energy deposition. These differences do not allow the extrapolation of our understanding of risks and mechanisms from terrestrial radiation exposure to that in space. Because there are no human epidemiological data for these radiation types, risk estimation must be generated from mechanistic details based on radiation physics and on molecular, cellular, tissue and organismal radiation biology related to exposure. Biologically significant data collected and compared to radiation type, dose, dose-rates, and energies provide valuable information to more effectively assess acceptable risk limits for astronauts on long-term space missions. Utilizing lung cancer mouse models (K-ras and EGFR), colon cancer susceptible mouse models (CPC;APC) and system biology approaches, our research is focused on obtaining relevant biological information on radiation-induced effects such as DNA damage/processing, signal transduction, cell cycle controls, cellular differentiation, and chronic inflammation. Our research is leading to quantitative assessments of radiation effects and a more comprehensive understanding of mechanism(s) involved in space radiation associated health risk so we can develop biological countermeasures to reduce these risks. Figure 2. (A) The KrasLA1 mouse model of lung tumorigenesis recapitulates many aspects of human lung cancer development and provides an invaluable tool to study disease etiology. (B) Utilizing lung cancer susceptibility models and system biology approaches, our research is focused on obtaining relevant biological information on radiation-induced effects.