BACKGROUND: Hyperproliferation of the colorectal mucosa is regarded as an early step in colorectal carcinogenesis. Deoxycholic acid, a secondary bile acid, stimulates colorectal epithelial proliferation in animals and is considered a tumor promoter in human colorectal carcinogenesis. The aim of this study was to investigate the correlation between colorectal mucosal proliferation and the serum deoxycholic acid level. METHODS: From each of 19 patients (10 men and 9 women) with (n = 3) or without (n = 16) colorectal adenoma, 18 biopsy specimens were obtained by colonoscopy, 3 from each of the 6 colonic segments. A crude nuclei fraction was prepared, and DNA was stained by propidium iodide to determine the proliferative index (the percentage of cells in the S and G2/M phases of the cell cycle) by flow cytometry. Serum levels of deoxycholic acid were determined by gas-liquid chromatography. RESULTS: The colonic proliferation rates (median of the values obtained in all segments, 14.1%; range, 10.0-18.7%) and the fasting serum deoxycholic acid levels (median, 0.86 micromol/L; range, 0.28-1.58 micromol/L) showed a significant correlation (r = 0.51, P = 0.03). Serum lithocholic, cholic, chenodeoxycholic, and ursodeoxycholic acid levels were not correlated with the proliferation rates. CONCLUSIONS: Levels of deoxycholic acid in serum are correlated with the rates of the colorectal mucosa. These results are consistent with the concept that deoxycholic acid promotes colorectal carcinogenesis.
BACKGROUND: Hyperproliferation of the colorectal mucosa is regarded as an early step in colorectal carcinogenesis. Deoxycholic acid, a secondary bile acid, stimulates colorectal epithelial proliferation in animals and is considered a tumor promoter in humancolorectal carcinogenesis. The aim of this study was to investigate the correlation between colorectal mucosal proliferation and the serum deoxycholic acid level. METHODS: From each of 19 patients (10 men and 9 women) with (n = 3) or without (n = 16) colorectal adenoma, 18 biopsy specimens were obtained by colonoscopy, 3 from each of the 6 colonic segments. A crude nuclei fraction was prepared, and DNA was stained by propidium iodide to determine the proliferative index (the percentage of cells in the S and G2/M phases of the cell cycle) by flow cytometry. Serum levels of deoxycholic acid were determined by gas-liquid chromatography. RESULTS: The colonic proliferation rates (median of the values obtained in all segments, 14.1%; range, 10.0-18.7%) and the fasting serum deoxycholic acid levels (median, 0.86 micromol/L; range, 0.28-1.58 micromol/L) showed a significant correlation (r = 0.51, P = 0.03). Serum lithocholic, cholic, chenodeoxycholic, and ursodeoxycholic acid levels were not correlated with the proliferation rates. CONCLUSIONS: Levels of deoxycholic acid in serum are correlated with the rates of the colorectal mucosa. These results are consistent with the concept that deoxycholic acid promotes colorectal carcinogenesis.
Authors: Betsy C Wertheim; Jeffrey W Smith; Changming Fang; David S Alberts; Peter Lance; Patricia A Thompson Journal: Cancer Prev Res (Phila) Date: 2011-11-04