Mucin-depleted foci are modulated by dietary treatments and show deregulation of proliferative activity in carcinogen-treated rodents.
The correlation between mucin-depleted foci (MDF) and colon carcinogenesis was studied in F344 rats initiated with 1,2-dimethylhydrazine and treated with a chemopreventive regimen (polyethylene glycol, PEG) or with a promoting diet (high-corn oil). High corn oil diet increased MDF, while PEG reduced them. The expression of p27 and p16, inhibitors of cyclin-dependent kinases, which inhibit the progression of the cell cycle, was studied by immunohistochemistry in MDF and in aberrant crypt foci (ACF) of control rats. In both MDF and ACF, the nuclear expression of p27 was markedly reduced, while p16 was reduced to a lower extent. Mitotic activity was higher in MDF and ACF than in normal mucosa of control rats. MDF were also identified in azoxymethane-initiated SWR/J mice. These results further confirm that MDF are preneoplastic lesions and could be useful biomarkers of colon carcinogenesis.
Femia
Angelo Pietro
AP
Department of Pharmacology, University of Florence, Florence, Italy.
Caderni
Giovanna
G
Bottini
Consuelo
C
Salvadori
Maddalena
M
Dolara
Piero
P
Tessitore
Luciana
L
D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D008297:Male; D009077:Mucins / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004041:Dietary Fats; D009077:Mucins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019813:1,2-Dimethylhydrazine