Dietary calcium and vitamin D modulate 1,2-dimethylhydrazine-induced colonic carcinogenesis in the rat.
To determine whether supplemental dietary calcium and/or vitamin D deficiency are involved in modulating colon cancer induced by 1,2-dimethylhydrazine (DMH), Sprague-Dawley rats were fed diets containing either: (a) a normal content of calcium (0.87%) and phosphorus (0.60%) with 2.2 IU of vitamin D3 per g of feed (group A); (b) the same diet as group A, but with calcium and phosphorus increased to 1.80 and 0.80%, respectively (group B); or (c) a vitamin D-deficient diet with supplemental calcium (1.80%) and phosphorus (0.80%) (group C). After 6 weeks on their respective diets, one-half the animals in each group were given s.c. injections of either vehicle or DMH (20 mg/kg body weight/week) for 26 weeks. Animals were then sacrificed and the incidence of tumors as well as the number of tumors per tumor-bearing rat were determined. Colonic mucosal polyamine levels were measured after 15 weeks of exposure to vehicle or DMH, before development of histologically recognizable neoplasms. The results of these experiments demonstrated that neither calcium supplementation alone nor supplemental calcium in conjunction with vitamin D deficiency altered the incidence of colonic cancer induced by this carcinogen. Supplemental calcium, however, significantly decreased the number of rats with multiple tumors and reduced tumor size. Moreover, vitamin D deficiency abolished these protective effects of calcium on colon cancer in this experimental model. DMH treatment increased polyamine levels in the premalignant colonic mucosa in group A rats. This carcinogen-induced effect was blunted by high dietary calcium. Vitamin D-deficient, calcium-supplemented rats (group C) showed an increase in N1-acetylspermidine, but not the other polyamines, with DMH treatment.
Sitrin
M D
MD
Department of Medicine, University of Chicago Hospitals and Clinics, Pritzker School of Medicine, University of Chicago, Illinois 60637.
Halline
A G
AG
Abrahams
C
C
Brasitus
T A
TA
D019813:1,2-Dimethylhydrazine; D000818:Animals; D002136:Calcium, Dietary / Q000008:administration & dosage* / Q000097:blood; D002273:Carcinogens; D003106:Colon / Q000737:chemistry; D003110:Colonic Neoplasms / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D004127:Dimethylhydrazines; D007413:Intestinal Mucosa / Q000737:chemistry; D008297:Male; D011073:Polyamines / Q000032:analysis; D051381:Rats; D014807:Vitamin D / Q000008:administration & dosage* / Q000097:blood
D002136:Calcium, Dietary; D002273:Carcinogens; D004127:Dimethylhydrazines; D011073:Polyamines; D014807:Vitamin D; D019813:1,2-Dimethylhydrazine