denuded tracheal grafts showed that secretory cells that were isolated with a cell sorter could reestablish an epithelium composed of basal, secretory, and ciliated cells. When pure populations of basal cells were used, only basal and ciliated cells were found in the repopulated graft. Those findings suggest that secretory cells can differentiate to form all the cell types in the trachea, whereas basal cells have more-limited capacity to differentiate. The observations that both cell types can divide and differentiate, point to the potential role of the secretory cell in radon-induced cancer induction.
The cells involved in radiation-induced tumors in the pulmonary parenchyma, as opposed to the airways, also are unidentified. Adenocarcinomas are thought to arise in the peripheral lung and display both mucous and serous cell differentiation. Bronchioloalveolar tumors, however, possess features of both Clara cells and alveolar type II cells. Clearly, cells can share common differentiation pathways during insult and the progression to cancer. These observations indicate that using tumor-cell structure as an indicator of the cells at risk in the peripheral lung might be misleading.
Robbins and Meyers (1995) have conducted extensive studies to define the cell populations in the human respiratory tract that are capable of cell division and thus might serve as the progenitor cells for respiratory tract cancer. They have determined that both basal and suprabasal cells are dividing in human tracheobronchial mucosa and that the suprabasal cells proliferate more frequently than the basal cells. From that observation, they developed a model that suggests two different stem-cell populations, which they call reserve stem cells (basal cells) and transient-amplifying stem cells. The transient-amplifying stem cells can, as demonstrated by Johnson and Hubbs (1990), give rise to all the different cell types, whereas the reserve stem cells renew the transient-amplifying stem-cell population and give rise to a narrower range of cell types.
A growing, although still small body of scientific literature suggests that the number of cells that respond to alpha-particle radiation is greater than the number of cells traversed by alpha particles. Hickman and colleagues (1994) found that exposure of lung-epithelial cells to small doses of alpha particles from a 238Pu source caused an increase in expression of the p53 gene in many more cells than were calculated to have been traversed. They concluded that the hit cells had communicated with the cell population and caused the remainder of the cells to respond. Thus, the target for interaction with alpha particles could be much larger than the cell nucleus.
It also has been demonstrated in both human and rodent cells that after exposure of cells to low doses of alpha particles, the number of cells with an increase in the frequency of sister-chromatid exchange (SCE) aberrations was larger than the number of cell nuclei traversed by alpha particles (Nagasawa and