Mucin-depleted foci (
MDF), formed by dysplastic crypts devoid of
mucins, have been identified in the colon of
carcinogen-treated rodents and in humans at high risk for
colon cancer. The lack of the protective layer of mucus may cause
inflammation which has been linked to colon
carcinogenesis, therefore, the expression of markers such as
cyclooxygenase-2 (COX-2),
inducible nitric oxide synthase (i-NOS) and macrophage infiltration was studied with immunohistochemistry (IH) in
MDF harvested from F344 rats treated with the colon
carcinogen 1,2-dimethylhydrazine (
DMH). The same determinations were performed in
aberrant crypt foci (ACF) and, at a later time point, in tumours. A dramatic increase in COX-2, i-NOS and macrophage infiltration was observed in
MDF but ACF showed a moderate increase compared with the paired normal mucosa. Tumours were positive for all the markers. RT-PCR experiments demonstrated that i-NOS
RNA expression was increased in a set of
MDF confirming the results obtained with immunohistochemistry. In an
inflammation-
cancer experimental model [mice treated with
azoxymethane (AOM) and
dextran sodium sulphate (DSS)], we observed that DSS-induced
inflammation promoted
MDF in a dose-dependent manner, whereas ACF were not affected. In conclusion, we report here for the first time a strong activation of the inflammatory process in
MDF, which may contribute to the further progression of
MDF to tumours.