Bile acid concentrations, cytotoxicity, and pH of fecal water from patients with colorectal adenomas.
In the multistage model of human colorectal tumorigenesis, both genetic and environmental factors play an important role. The identity of the environmental factors involved, however, still remains to be elucidated. As fecal bile acids are proposed as candidates, we compared the concentration of bile acids in fecal water from patients at different risk of developing colorectal cancer. In addition, pH of fecal water as well as its cytotoxicity to HT-29 colonic cells was determined. The high-risk group consisted of individuals diagnosed with one or more (tubulo)villous colorectal adenomas larger than 1 cm in diameter and containing moderate or severe dysplasia (N = 20). Subjects with colorectal adenomas smaller than 1 cm and showing only minor dysplasia were assigned to the medium risk group (N = 19). The control group consisted of persons with normal findings by colonoscopy (N = 25). The results show no significant differences in fecal water bile acid concentrations between the three groups. However, 46% of the observed cytotoxicity is explained in a regression model that includes pH and the concentrations of deoxycholic acid, cholic acid, and ursodeoxycholic acid. The pH of fecal water is found to be significantly lower in the high risk group as compared to the controls, suggesting that a relatively high fecal pH has a protective effect on the development of colorectal adenomas. Although hyperproliferation as a result of cytotoxicity has been suggested to contribute to tumor formation in the colon, the pH-dependent cytotoxicity of bile acids in fecal water was not found to be associated with adenoma formation in the present study.
de Kok
T M
TM
Department of Health Risk Analysis and Toxicology, Universiteit Maastricht, The Netherlands.
van Faassen
A
A
Glinghammar
B
B
Pachen
D M
DM
Eng
M
M
Rafter
J J
JJ
Baeten
C G
CG
Engels
L G
LG
Kleinjans
J C
JC
D000236:Adenoma / Q000378:metabolism*; D018253:Adenoma, Villous / Q000378:metabolism; D001647:Bile Acids and Salts / Q000032:analysis*; D001834:Body Water / Q000737:chemistry*; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000378:metabolism*; D005243:Feces / Q000737:chemistry*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D012004:Rectal Neoplasms / Q000378:metabolism*; D018570:Risk Assessment
D001647:Bile Acids and Salts