CHEMOPREVENTION OF AZOXYMETHANE-INDUCED COLON-CANCER BY ASCORBYLPALMITATE, CARBENOXOLONE, DIMETHYLFUMARATE AND P-METHOXYPHENOL IN MALE F344RATS

The chemopreventive effect of 40 and 80% maximum tolerated dose (MTD) levels of ascorbylpalmitate (AP), carbenoxolone (CBX), dimethylfumarat e (DMF) and p-methoxyphenol (p-MP) administrated in the diet before an d during initiation and postinitiation phases of azoxymethane (AOM)-in duced colon carcinogenesis was studied in male F344 rats. The MTD leve ls of AP, CBX, DMF and p-MP were determined in male F344 rats and foun d to be 5000 1500, 1000 and 1000 ppm, respectively, in modified AIN-76 A diet. Based on these MTD vales, 40 and 80% MTD levels of each agent was tested for their efficacy in color carcinogenesis. At 5 weeks of a ge, groups of animals were fed the control (modified AIN-76A diet. Bas ed on these MTD values, 40 and 80% MTD levels of each AP. CBX. DMF and p-MP. At 7 weeks of age, all animals, except those in the vehicle (no rmal saline)-treated groups, were given two weekly s.c. injections of AOM at a dose rate of 15 mg/kg body weight/week. All groups were conti nued on their respective dietary regimen until the termination of the experiment 52 weeks after the carcinogen treatment. Colonic tumors wer e evaluated histopathologically. The results indicate that dietary adm inistration of 40% MTD of AP significantly inhibited multiplicities (t umor/animal) of noninvasive and total (invasive plus noninvasive) aden ocarcinoma of the color (P < 0.05) and 80% MTD of AP significantly inh ibited the incidence (% animals with tumors) and the multiplicities of invasive and total adenocarcinomas of the colon (P < 0.01). Dietary C BX at 40 and 80% MTD levels suppressed the incidence and multiplicitie s of invasive and total adenocarcinomas (P < 0.05 to 0.001) whereas 40 and 80% MTD of DMF and p-MP had significantly inhibited invasive aden ocarcinomas incidence and multiplicity (P < 0.05 to 0.001). However, D MF and p-MP had no significant effect on noninvasive and total adenoca rcinoma incidence and multiplicity (P > 0.05). These results suggests that AP and CBX posses potential chemopreventive properties against co lon cancer