Carcinogenesis, Vol 18, 465-472, Copyright © 1997 by Oxford University Press
I Thorup
Many studies have been conducted to assess the potential preneoplastic
nature of colonic aberrant crypt foci (ACF), but still the biological
significance of these foci and their relationship to colon neoplasia
remains to be elucidated. In the present paper a battery of variables
suggested to be indicative for colon cancer development has been studied in
relation to ACF in rats. These include: (i) the degree of dysplasia; (ii)
the type of mucus production; (iii) the cellular immunohistochemical
expression and distribution of transforming growth factors alpha and beta
and their respective receptors, epidermal growth factor receptor and
transforming growth factor beta receptors I and II and phosphorylated
cellular tyrosine. The parameters have been investigated in ACF selected
from a previous study where the foci were induced under different
circumstances, leading to disparities in the number as well as the crypt
multiplicity obtained. The present study showed that for all parameters
investigated, apart from sialomucin production, the different experimental
conditions had no effect on the individual ACF, irrespective of the number
and distribution of the different categories of ACF among the various
diets. However, it was shown that the degree of dysplasia correlated
strongly with crypt multiplicity and that all the investigated ACF lacked
expression of transforming growth factor alpha and expressed a reduced
amount of transforming growth factor beta compared with normal crypts.
These observations may indicate that ACF are preneoplastic lesions and
supports the suggestion that they may, at least in the rat, have the
potential to gradually progress to tumors, but no single ACF showed
particular characteristics indicating specific proneness to tumor
development. The study could not confirm the presence of sialomucin-
producing ACF as a valid marker for tumor development.
ARTICLES
Histomorphological and immunohistochemical characterization of colonic aberrant crypt foci in rats: relationship to growth factor expression
Institute of Toxicology, National Food Agency, Soborg, Denmark.
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