Aberrant crypt foci (ACF) and
mucin-depleted foci (
MDF) have recently been recognized as pre-neoplastic lesions in the colon of
carcinogen-treated rodents. In the present study, we analyzed the sequential development of ACF and
MDF histopathologically in the colon of rats from 5 to 40 weeks after
DMH treatment. The numbers of ACF per colon increased over time during the experiment, and were much higher than the number in
tumors, while the number of
MDF per colon remained unchanged from the early stage (the 5th week after
carcinogen exposure), and approximate to those in
tumors. The incidence of ACF, which was much higher than that of
tumors, also increased gradually in a time-dependent manner. The incidence of
MDF, however, was similar to that of
tumors and did not change significantly during the whole experiment. No lesion as dysplasia with high-grade (DHG) or
adenocarcinoma (AC) were found in any large ACF from the 5th to 40th week histopathologically, whereas all of the large
MDF showed DHG or AC features. Even at 5 weeks,
MDF showed features of DHG. We classified these into two forms of
MDF: flat and protruded
MDF. At 40 weeks, the number of flat
MDF per colon decreased significantly compared with that at 20 weeks (p<0.05), however, the number of protruded
MDF per colon increased (p<0.01), and the percentage of DHG in a protruded
MDF lesion decreased but that of AC increased remarkably. In conclusion,
MDF may develop into
cancer through the so-called 'de novo
cancer' pathway.