The fractions of respiratory tract cells at risk in formaldehyde carcinogenesis

Abstract

Clonal growth modeling of carcinogenesis requires data on the number of cells at risk of becoming cancerous. We synthesized literature data to estimate the fraction of respiratory tract epithelial cells that are progenitor cells, and therefore at risk, in formaldehyde carcinogenesis for specific respiratory tract regions. We concluded that the progenitor cells for the transitional and respiratory epithelia of the nose are basal and nonciliated cells and Type II cells in the alveolar region. In the conducting airways, our evaluation indicated that ciliated and basal cells are not in the progenitor pool. Respiratory tract epithelial cell fractions of 0.819 in rats and 0.668 in humans were estimated from the data. The total numbers of epithelial cells in the lower respiratory tract of humans and rats were allocated to individual generations. Cell cycle times were also estimated from literature data, since the reciprocal of cell cycle time is an important variable in clonal growth modeling. Sensitivity analyses of a previously published risk model for formaldehyde carcinogenesis showed that specification of the fraction of cells at risk markedly affects estimates of some parameters of the clonal growth model. When all epithelial cells are considered part of the progenitor pool, additional risks for the non-smoking population was typically over predicted by about 35% for high exposure levels. These results demonstrate the importance of accurately identifying cell populations at risk when applying quantitative models in risk assessments.

Keywords::

• respiratory tract cells
• carcinogenesis
• risk
• formaldehyde
• humans
• rats

Acknowledgements

Some information and data in the current paper also appear in CIIT (1999) and are used with permission. The authors wish to acknowledge the excellent assistance of Ms. Jeanne Galbo, deceased, in the preparation of the manuscript. The United States Environmental Protection Agency through its office of Research and Development collaborated in the research described here. It has been subjected to Agency review and approved for publication.

Declaration of interest

At the time this research was initiated, all authors except Dr. Overton were employees of the Hamner Institute for Health Sciences. The Hamner Institute was funded by the Long Range Research Initiative program of the American Chemistry Council as well as a number of smaller sponsors.