A computer model of oxygen dynamics in human colon mucosa: implications in normal physiology and early tumor development.

Based on the geometry of the colon mucosa, we built a model to compute the oxygen supply, the oxygen diffusion across the interstitial matrix, and the oxygen consumption by cryptal and stromal cells. By using an iterative algorithm, we have been able to solve a set of discretized (time and space) oxygen balance equations and determine the three-dimensional distribution of pO(2) in the mucosa. Although significant longitudinal and radial pO(2) variations were found, cells appeared to operate at their maximum respiratory capacity, regardless of their location in the tissue. The estimated oxygen extraction fraction was 47%, while the capillary oxygen permeability was 1.57 x 10(-5) cm m s(-1). We concluded that cellular metabolism in normal colon mucosa is not limited by oxygen supply, thus prompting the idea that oxygenation does not determine the characteristic microenvironments occurring along the normal Lieberkhün crypts. In an extended model, simulation of an aberrant crypt focus (ACF)--the earliest stage in the adenomatous polyp-carcinoma sequence--showed instead that respiratory activity decreased when the capillary array symmetry is disrupted due to the ACF growth. A unified explanation about the alternative of a hypoxic-independent and/or a hypoxic-dependent early angiogenic response associated to the development of ACF is proposed.