Effect of calcium on azoxymethane-induced aberrant crypt foci and cell proliferation in the colon of rats.
Calcium has been proposed for prevention of colon cancer. The effects of calcium on azoxymethane (AOM)-induced aberrant crypt foci (ACP), a putative precancerous lesion, and cell proliferation were determined in rat colon. Male F344 rats were given AIN-76A diet that contained calcium at concentrations of 0.5, 1.0, 2.5, 5.0, 10.0 and 15.0 g/kg in experiment 1 and 0.2, 2.0 and 6.0 g/kg in experiment 2. One week after the rats received these diets, they were given the first of two weekly 15 mg/kg injections of AOM. The rats were killed after 35 days of exposure to the different diets. In experiment 1, exposure to either low (0.5 and 1.0 g/kg) or high (10.0 and 15.0 g/kg) concentrations of calcium reduced the yield of ACF relative to 5.0 g/kg calcium. In experiment 2, exposure to 0.2 and 2.0 g/kg calcium resulted in a lower yield of ACF than 6.0 g/kg. Cell proliferation in ACF and non-involved crypts was reduced in animals that received 0.5 or 15.0 mg/Kg relative to 5.0 mg/kg diet calcium. Our results indicate that both lower and higher concentrations of calcium relative to its standard concentration in AIN-76A diet can prevent ACF and reduce the extent of cell proliferation in the lesion which would likely lead to the prevention of colon cancer.
Li
H
H
Medical College of Ohio, Department of Pathology, Toledo 43614-5806, USA.
Kramer
P M
PM
Lubet
R A
RA
Steele
V E
VE
Kelloff
G J
GJ
Pereira
M A
MA
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001397:Azoxymethane; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000627:therapeutic use*; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D012307:Risk Factors
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D001397:Azoxymethane; D002118:Calcium