Histomorphological and immunohistochemical characterization of colonic aberrant crypt foci in rats: relationship to growth factor expression.
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.
Thorup
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Institute of Toxicology, National Food Agency, Soborg, Denmark.
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D004043:Dietary Fiber / Q000008:administration & dosage / Q000494:pharmacology; D019422:Dietary Sucrose / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009077:Mucins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017978:Receptors, Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics; D052116:Sialomucins; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D004041:Dietary Fats; D004043:Dietary Fiber; D019422:Dietary Sucrose; D006133:Growth Substances; D009077:Mucins; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D052116:Sialomucins; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; C012564:sulfomucin; D066246:ErbB Receptors; C029310:lard