Effects of Radiation Exposure on Lung Carcinogenesis
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Lung cancer is one of the most prevalent forms of cancer in both men and women with over 1.3 million annual related deaths worldwide. Analysis of several human populations exposed to radiation reveals that the lung is remarkably susceptible to the carcinogenic effects of radiation exposure. The considerable lung surface area and slow rate of epithelial turnover may have causal roles in this vulnerability. This may be due to the increased probability that a progenitor cell of the lung, which is proposed to be the cancer-initiating cell, may acquire multiple carcinogenic alterations from radiation exposure. Currently, the lung is believed to have several facultative progenitor cells, situated throughout the lung epithelium, that are regionally restricted in their regenerative capacity. Normal human bronchial epithelial cells (HBECs), immortalized through the expression of Cdk4 and hTERT, provide a sustainable cell reagent for the evaluation of the radiation effects in vitro. These HBECs retain a novel multipotent capacity in vitro (capable of differentiating into both central and peripheral lung cell types) and thus may represent an unrestricted progenitor of the adult lung that resembles an embryonic progenitor. Studies to determine whether the differentiation state influences radiation exposure effects, such as DNA damage and repair, are ongoing. As cellular responses change upon the acquisition of oncogenic mutations, the effects of fractionated or acute radiation exposure on lung carcinogenesis in vivo were determined utilizing the transgenic LA1 K-ras mouse model of lung cancer compared to wildtype littermates. Radiation-induced carcinogenesis is a major concern not only for cancer patients being treated with therapeutic radiation but also for astronauts on long-term space missions. X-ray radiation did not affect the incidence or progression of lung carcinogenesis in this mouse model of lung cancer. High-energy 56Fe- particle irradiation (a type of radiation present in deep space), however, significantly increased the incidence of invasive carcinoma when administered as a fractionated dose but not as a single acute dose. These results demonstrate that pre-initiated lesions may be more susceptible to malignant transformation upon exposure to radiation. Thus, radiation may have an impact on both lung cancer initiation and progression.