Chemoprevention of azoxymethane-induced colon cancer by ascorbylpalmitate, carbenoxolone, dimethylfumarate and p-methoxyphenol in male F344 rats.
The chemopreventive effect of 40 and 80% maximum tolerated dose (MTD) levels of ascorbylpalmitate (AP), carbenoxolone (CBX), dimethylfumarate (DMF) and p-methoxyphenol (p-MP) administrated in the diet before and during initiation and postinitiation phases of azoxymethane (AOM)-induced colon carcinogenesis was studied in male F344 rats. The MTD levels of AP, CBX, DMF and p-MP were determined in male F344 rats and found to be 5000 1500, 1000 and 1000 ppm, respectively, in modified AIN-76A diet. Based on these MTD values, 40 and 80% MTD levels of each agent was tested for their efficacy in color carcinogenesis. At 5 weeks of age, groups of animals were fed the control (modified AIN-76A diet or diets containing 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 (normal 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 continued on their respective dietary regimen until the termination of the experiment 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. The results indicate that dietary administration of 40% MTD of AP significantly inhibited multiplicities (tumor/animal) of noninvasive and total (invasive plus noninvasive) adenocarcinoma of the colon (P < 0.05) and 80% MTD of AP significantly inhibited the incidence (% animals with tumors) and the multiplicities of invasive and total adenocarcinomas of the colon (P < 0.01). Dietary CBX at 40 and 80% MTD levels suppressed the incidence and multiplicities 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 adenocarcinoma incidence and multiplicity (P < 0.05 to 0.001). However, DMF and p-MP had no significant effect on noninvasive and total adenocarcinoma incidence and multiplicity (P > 0.05). These results suggest that AP and CBX possess potential chemopreventive properties against colon cancer.
Rao
C V
CV
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, New York 10595, USA.
Rivenson
A
A
Kelloff
G J
GJ
Reddy
B S
BS
D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001397:Azoxymethane / Q000633:toxicity; D002229:Carbenoxolone / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D000069462:Dimethyl Fumarate; D005650:Fumarates / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D000840:Anisoles; D016588:Anticarcinogenic Agents; D005650:Fumarates; C009760:mequinol; D000069462:Dimethyl Fumarate; D002229:Carbenoxolone; D001397:Azoxymethane; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid