Determine Key Events in Radiation-Induced Lung Cancer on Earth and During Space Flight

Lung cancer is the leading cause of cancer death in both women and men in the U.S.A. and in the Western world. While lung cancer is caused mostly by smoking exposure, a significant number of lung cancers arise in lifetime never smokers and thus is a sizable health problem in the USA.

A major underlying question has been the role of other environmental carcinogens, especially environmental radiation. These include radon gas in the environment (e.g. soil beneath homes), or the widespread use of repeated CT scans for lung cancer screening. Radiation is a known carcinogenic influence but the molecular events in lung epithelial cells in response to radiation need to be determined.

Radiation is also a major concern for astronauts on long-term space missions. Exposure to galactic cosmic radiation is predicted to carry a significant risk of cancer development, particularly in the lung because of its large surface and thus higher radiation exposure compared to other organs.

We have been studying the effect of both Earth (gamma radiation) and space (high energy particle radiation) in human bronchial epithelial cells (HBECs) and mouse transgenic models of lung cancer. We have discovered long term molecular correlates of these exposures and the important role such radiation could have on lung cancer development.

Specifically, we are improving the understanding of space radiation in lung cancer initiation, promotion and progression; we are investigating the increased risk from space radiation as a function of age, latency, gender, tissue, radiation quality, and dose rate; we are developing tissue-specific risk models using human 2D and 3D culture as well as animal models for lung cancer; we are investigating how aberrant DNA damage processing, genomic instability, epigenetic effects, persistent oxidative damage, and non-targeted effects contribute to irradiation-associated lung cancer. All these findings have large implications both for predicting cancer risk following long-term space flight, and for predicting the effect of CT screening on Earth.

This NSCOR project is a multi-investigator collaboration with Dr. Minna (PI), Drs. Jerry Shay (Dept. of Cell Biology), Michael Story, David Chen, and Aroumougame Asaithamby (Dept. of Radiation Oncology), and Yang Xie (Dept. of Clinical Sciences, Biostatistics).