Sucrose enhancement of the early steps of colon carcinogenesis in mice.
The association of refined sugars and colorectal cancers and polyps in three recent case-control studies led us to investigate the effects of sucrose, fructose and glucose on colonic epithelial proliferation and sensitivity to carcinogenesis. CF1 and C57BL/6J mice were used; proliferation was assessed as vincristine-accumulated mitotic figures per crypt section; sensitivity to carcinogenesis was assessed as the number of aberrant crypt foci (ACF) per colon observed following the colon carcinogen, azoxymethane (AOM, 3 mg/kg and 5 mg/kg). Oral gavages of sucrose and fructose in CF1 mice (10 g/kg) increased colonic proliferation 16 h later (2.8 +/- 0.6 and 4.1 +/- 0.7 (mean +/- SEM) accumulated mitotic figures/crypt section), compared with glucose and water (1.0 +/- 0.2 and 0.4 +/- 0.1). Sucrose and fructose given 14 h prior to the AOM (5 mg/kg) increased the sensitivity of the colon to carcinogenesis (18.4 +/- 1.5 and 13.1 +/- 1.8 ACF/colon), compared with glucose and water (11.4 +/- 2.0 and 8.6 +/- 1.1). Similar results were observed with C57BL/6J mice. We conclude that dietary sucrose and fructose may represent risk factors for colorectal cancer through a direct effect of the sugars on colonic epithelial proliferation.
Stamp
D
D
Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Zhang
X M
XM
Medline
A
A
Bruce
W R
WR
Archer
M C
MC
D000818:Animals; D001397:Azoxymethane; D002455:Cell Division / Q000187:drug effects; D003043:Cocarcinogenesis; D003110:Colonic Neoplasms / Q000139:chemically induced*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects; D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced*; D013045:Species Specificity; D013395:Sucrose / Q000008:administration & dosage / Q000009:adverse effects*
D005632:Fructose; D013395:Sucrose; D005947:Glucose; D001397:Azoxymethane