The cell types and normal turnover rate in respiratory tract cells vary by the region of the respiratory tract and the cell type involved (Adamson 1985). Changes in cell kinetics in the respiratory tract have been demonstrated after internal deposition of radioactive materials (Sanders and others 1989), external radiation exposure (Adamson 1985), and inhalation of radon (Atencio 1994; Bisson and others 1994; Taya and others 1994).

Taya and colleagues (1994) demonstrated an increase in the labeling index (which reflects the proportion of cells synthesizing DNA) as a function of exposure at 0.42–3.465 Jhm-3 (120–990 WLM) in rat alveolar, bronchiolar, bronchial, and tracheal epithelial cells over a range of times after exposure. The maximal increase in proliferation was at 14 days for all 4 regions of the respiratory tract. In studies of the nose and upper respiratory tract, Atencio (1994) demonstrated a similar time-dependent increase in cell proliferation after exposure to 0.595 Jhm-3 (170 WLM) of radon progeny. The labeling index increased after the end of the exposure to a peak between 14 and 50 days and then returned nearly to background levels. The increase was observed only in the trachea, the nasal septum, and the middle section of the larynx. Several of these regions were calculated to have high deposition for vapors (Kimbell and others 1993) and small particles (James 1994). In rats, the bronchial region, which is calculated to be at greatest risk for cancer induction, also receives the highest dose and responds with the highest cell-proliferation response to inhaled radon. Overall, the findings suggest a relationship between initial dose and changes in cell proliferation.

However, in considering these results, it is important to recognize that overall exposure rates differ widely; in studies of rats, a few weeks to months, in miners, a few years to about half the lifetime, and in residential exposures, a lifetime.

Radon-induced tissue damage and cell killing increases cell turnover to replace damaged cells (Taya and others 1994). This radon-induced increase in cell proliferation can result in repair of tissue damage. Apoptosis can eliminate damaged cells directly and normal and enhanced cell proliferation can also eliminate damaged cells at mitosis (Carrano and Heddle 1973) potentially reducing the risk for cell transformation and cancer. On the other hand, changes in cell kinetics have the potential to increase clonal expansion of altered or mutated cells increasing risk. Cell proliferation is a required step during cancer induction without which cancer cannot form, thus, enhanced cell proliferation can be viewed as a mechanism of either tissue repair or promotion of the cancer process.

CELLS AT RISK

To determine the dose, energy distribution, and cellular processes essential for radon-induced carcinogenesis, it is important to identify the respiratory tract cells at risk from radon exposure. In radon-inhalation studies, the cells of the



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