Title
The regulation of cell proliferation and differentiation in intestinal epithelium. II. A quantitative histochemical and autoradiographic study after low doses of X-irradiation
Author
Medisch Biologisch Labortorium TNO
Galjaard, H.
Bootsma, D.
Publication year
1969
Abstract
To investigate the biochemical mechanisms involved in the regulation of cell proliferation and differentiation the intestinal epithelium has been chosen because of the regular distribution of proliferative-, non-dividing maturing- and functional cells along the crypt and villus. The effect of low doses of irradiation (50-400 R) which selectively influences the pool of proliferating cells was studied using quantitative histochemical techniques for enzyme assays in the various cell compartments and 3H-thymidine labelling with subsequent autoradiography to determine the localisation of the proliferating cells and the migration rate of the cells along crypt and villus. In normal crypt and villus the activity of the group of non-specific esterases was the only group of enzymes tested of which the activity was quite different in the various cell compartments. Hardly any activity was present in the proliferating cells, a higher activity in the non-dividing maturing crypt cells and a very high activity in the functional cells of the villus. After irradiation the esterase activity in the crypt was markedly reduced and the duration of this effect and the number of crypt cells involved appeared to be clearly related to an increase in the pool of proliferating cells. While in the normal crypt the proliferating cell makes a "critical decision" to enter the non-dividing maturing-cell compartment about halfway along the length of the crypt, during the period of recovery from irradiation the cell appears to be able to postpone this decision and many do not stop proliferation until the functional compartment of the villus has been reached. The continuation of cell proliferation is always accompanied with a loss of esterase activity. As after irradiation the pool of proliferating cells has increased at the expense of the maturing cell compartment and the migration rate of the cells has been found not to be influenced, cells with reduced esterase activity will enter the functional compartment of the villus. Microchemical analyses of various parts of a single villus showed that no changes in enzyme activity occur while the functional cells are moving upwards along the villus. Experimental results are discussed in relation to the problem of the critical decision phase in the crypt, the possible role of esterase activity as a marker for cell differentiation and the functional implications of changes in the proliferative and maturing-cell compartments. © 1969.
Subject
Esterase
Thymidine
Tritium
Animal
Autoradiography
Cell differentiation
Cell division
Cytochemistry
Cytology
Duodenum
Enzymology
Epithelium
Freeze drying
Intestine mucosa
Male
Metabolism
Radiation exposure
Radiation response
Rat
Time
Histocytochemistry
Intestinal Mucosa
Male
Radiation Effects
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TNO identifier
227137
ISSN
0014-4827
Source
Experimental Cell Research, 58 (58), 79-92
Document type
article