The fractions of respiratory tract cells at risk in formaldehyde carcinogenesis.


Journal Article

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.

Full Text

Cited Authors

  • Miller, FJ; Kimbell, JS; Preston, RJ; Overton, JH; Gross, EA; Conolly, RB

Published Date

  • October 2011

Published In

Volume / Issue

  • 23 / 12

Start / End Page

  • 689 - 706

PubMed ID

  • 21888524

Pubmed Central ID

  • 21888524

Electronic International Standard Serial Number (EISSN)

  • 1091-7691

International Standard Serial Number (ISSN)

  • 0895-8378

Digital Object Identifier (DOI)

  • 10.3109/08958378.2011.603190


  • eng