Abstract Crypt foci with absent or scant mucous production (mucindepleted foci, MDF) were recently described by our group in the colon of azoxymethane (AOM)-treated rats. Since MDF are dysplastic and easy to quantify, we think that MDF are pre-neoplastic lesions that could be used as biomarkers for carcinogenesis. To test this hypothesis, we studied MDF in azoxymethane (AOM)-initiated rats treated with cholic acid (CHA), a promoter of colon carcinogenesis or with piroxicam (PXC), a colon cancer-inhibiting drug. Aberrant crypt foci (ACF) were determined as well. F344 male rats were treated with AOM (15 mg/kg _ 2, s.c.) and then divided into: controls, which were fed AIN76 diet; CHA group, which was fed AIN76 diet containing CHA 0.5% w/w; PXC group, which was fed AIN76 diet containing PXC 0.02% w/w. Ten weeks after the first dose of AOM, the total number ofMDF was significantly increased in rats treated with CHA (P50.05) and drastically reduced (P50.01) in rats treated with PXC (MDF/colon were 6.10 _ 1.26, 10.59 _ 1.96 and 1.31 _ 0.21 in controls, CHA and PXC groups, respectively, means _ SE). The multiplicity of MDF was also increased in CHA-treated rats. On the contrary, ACF multiplicity was significantly decreased by CHA. In PXC-treated rats there were fewer ACF with lower multiplicity. The effect of PXC was also investigated 15 weeks after the first AOM dose and the results showed that the total number of MDF in the PXC group was significantly lower than in controls. The number of `large' MDF, formed by 12 or more crypts, was also reduced (P50.01) byPXC (`large'MDF were 1.7_0.5 and 0.4 _ 0.2 in control and PXC groups, respectively). Since CHA promotes and PXC reduces colon cancer, MDF are correlated with carcinogenesis and can be proposed as endpoints to study the modulation of colon carcinogenesis in short-term experiments.

MUCIN-DEPLETED FOCI (MDF) IN AZOXYMETHANE (AOM)-INDUCED RATS TREATED WITH CHOLIC ACID (CHA) OR PIROXICAM (PXC) AS USEFUL BIOMARKERS OF COLON CARCINOGENESIS / G. CADERNI; P. DOLARA; A. P. FEMIA. - In: CARCINOGENESIS. - ISSN 0143-3334. - STAMPA. - 25(2004), pp. 277-281.

MUCIN-DEPLETED FOCI (MDF) IN AZOXYMETHANE (AOM)-INDUCED RATS TREATED WITH CHOLIC ACID (CHA) OR PIROXICAM (PXC) AS USEFUL BIOMARKERS OF COLON CARCINOGENESIS.

CADERNI, GIOVANNA;DOLARA, PIERO;
2004

Abstract

Abstract Crypt foci with absent or scant mucous production (mucindepleted foci, MDF) were recently described by our group in the colon of azoxymethane (AOM)-treated rats. Since MDF are dysplastic and easy to quantify, we think that MDF are pre-neoplastic lesions that could be used as biomarkers for carcinogenesis. To test this hypothesis, we studied MDF in azoxymethane (AOM)-initiated rats treated with cholic acid (CHA), a promoter of colon carcinogenesis or with piroxicam (PXC), a colon cancer-inhibiting drug. Aberrant crypt foci (ACF) were determined as well. F344 male rats were treated with AOM (15 mg/kg _ 2, s.c.) and then divided into: controls, which were fed AIN76 diet; CHA group, which was fed AIN76 diet containing CHA 0.5% w/w; PXC group, which was fed AIN76 diet containing PXC 0.02% w/w. Ten weeks after the first dose of AOM, the total number ofMDF was significantly increased in rats treated with CHA (P50.05) and drastically reduced (P50.01) in rats treated with PXC (MDF/colon were 6.10 _ 1.26, 10.59 _ 1.96 and 1.31 _ 0.21 in controls, CHA and PXC groups, respectively, means _ SE). The multiplicity of MDF was also increased in CHA-treated rats. On the contrary, ACF multiplicity was significantly decreased by CHA. In PXC-treated rats there were fewer ACF with lower multiplicity. The effect of PXC was also investigated 15 weeks after the first AOM dose and the results showed that the total number of MDF in the PXC group was significantly lower than in controls. The number of `large' MDF, formed by 12 or more crypts, was also reduced (P50.01) byPXC (`large'MDF were 1.7_0.5 and 0.4 _ 0.2 in control and PXC groups, respectively). Since CHA promotes and PXC reduces colon cancer, MDF are correlated with carcinogenesis and can be proposed as endpoints to study the modulation of colon carcinogenesis in short-term experiments.
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G. CADERNI; P. DOLARA; A. P. FEMIA
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/15347
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