Latent Time (Quiescence) Properties of Human Colonic Crypt Cells : Mechanistic Relationships to Colon Cancer Development
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2017, Vol 1, Issue 4
Abstract
Objectives : To determine latent time (quiescence) properties of human colonic crypt cells and explores relationships between these properties and Colorectal Cancer (CRC) development. Methods : Quantitative methods were developed to calculate latent time1 (latenzzeit) of colonic cells at each position along the crypt axis and to evaluate available data on total cell cycle times for human normal, familial adenomatous polyposis (FAP), and adenomatous crypts. Results : Our analysis of normal colonic data revealed that latenzzeit decreases from crypt base to top. Moreover, alogarithmic plot of latenzzeit versus crypt position was non-linear, but was equal to sum of three lines showing that latenzzeit has three components (slow, medium fast). A similar plot of FAP data was on linear and equal to sum of three lines, but slopes and intercepts were not equal to results for normal crypts. A logarithmic plot of adenomatous crypt data was linear showing loss of two latenzzeit components (slow & fast) and retention of one (medium) component. Conclusions : Our data indicate that, in normal crypts, latenzzeit is regulated by three sequential, first order kinetic processes. Quantifying latenzzeit in neo-plastic crypts provides a measure of the effects of APC mutations in CRC development. In FAP crypts, heterozygous APC mutation modifies latenzzeit by affecting all three kinetic processes. In adenomatous crypts, homozygous mutant APC modifies latenzzeit through loss of two and modification of the third process. Latenzzeit also explains control of total cell cycle time. In normal crypts, the decrease in total cell cycle time along the crypt axis can be attributed to decrease in latenzzeit from crypt base to top. In neo-plastic crypts, changes in latenzzeit explain progressive lengthening of the total cell cycle time along the axes of FAP and adenomatous crypts. Thus, latenzzeit regulatory mechanisms appear essential for crypt maintenance and, when altered, contribute to development of CRC.
Authors and Affiliations
Olaf A Runquist, Rachel Mazac, Bruce M Boman
Keywords
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- EP ID EP571546
- DOI 10.26717/BJSTR.2017.01.000386
- Views 142
- Downloads 0
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