Colonic epithelial cell proliferation in a rat model of nongenotoxin-induced colonic neoplasia.
BACKGROUND
The effect on colonic cell proliferation of poligeenan, a nongenotoxic polysaccharide that induces colon tumors in rats, was compared with guar gum and carrageenan.


METHODS
Fischer 344 rats were fed a basal diet supplemented with carrageenan and poligeenan fibers for up to 91 days. The quantitative levels of proliferation, location of the proliferating cells, and the ability of the mucosa to readapt by removing the experimental fibers from the diet were tested.


RESULTS
The mucosal epithelium exhibited a 5-fold increase in thymidine kinase activity in both the carrageenan and poligeenan groups. Proliferating cells appeared at the luminal surface only in the poligeenan-treated rats, and the number of proliferating cells in the upper third of the crypt increased 35-fold. A second and third set of animals were fed one of the three test diets for either 28 or 64 days, followed by a 28-day recovery period. Proliferation in the guar- and carrageenan-treated groups returned to basal levels. In poligeenan-treated rats, thymidine kinase levels, and proliferating cells in the upper third of the crypt remained 2- and 11-fold, respectively, above controls.


CONCLUSIONS
The difference in recovery time between the poligeenan group and the others, and the luminal location of proliferating cells may prove useful as markers in understanding early events in the carcinogenic process induced by a nongenotoxin.
Wilcox
D K
DK
Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio.
Higgins
J
J
Bertram
T A
TA
D000284:Administration, Oral; D000818:Animals; D002351:Carrageenan / Q000008:administration & dosage / Q000032:analysis*; D002455:Cell Division; D003106:Colon / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000737:chemistry / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D005685:Galactans / Q000008:administration & dosage / Q000009:adverse effects*; D007150:Immunohistochemistry; D008351:Mannans / Q000008:administration & dosage / Q000009:adverse effects*; D009687:Nuclear Proteins / Q000032:analysis; D053149:Plant Gums; D011134:Polysaccharides / Q000008:administration & dosage / Q000009:adverse effects*; D018809:Proliferating Cell Nuclear Antigen; D051381:Rats; D011916:Rats, Inbred F344; D013937:Thymidine Kinase / Q000032:analysis
D005685:Galactans; D008351:Mannans; D009687:Nuclear Proteins; D053149:Plant Gums; D011134:Polysaccharides; D018809:Proliferating Cell Nuclear Antigen; C014157:poligeenan; D002351:Carrageenan; C007894:guar gum; D013937:Thymidine Kinase