Serum bile acids, programmed cell death and cell proliferation in the mucosa of patients with colorectal adenomas

Abstract

Background. Deoxycholic acid induced programmed cell death and an imbalance with cell proliferation may favour colorectal tumourigenesis according to ‘in vitro’ studies, but information is lacking on the relationships occurring ‘in vivo’ in humans. Aims. To evaluate whether serum deoxycholic acid is associated with programmed cell death and cell proliferation in colonic mucosa. Methods. In 10 patients with colorectal adenomas, we measured fasting serum levels of bile acids; and, in normal colonic mucosa, programmed cell death by the TUNEL technique and cell proliferation by immunohistochemical staining with anti-Ki67. Total and compartmental indices for both activities were calculated. Results. Among serum bile acids, only total deoxycholic acid (median: 0.89 μmol/L ±0.54 95% CI), showed a significant positive correlation with the total and basal compartments PCD Index ( r = 0.68, p < 0.05). Total proliferation index showed no correlation with either total PCD Index, or bile acids. Within the median compartment of the crypt, cell proliferation was negatively associated with all unconjugated bile acids. Conclusions. The positive association between deoxycholic acid and programmed cell death in the basal compartment of the crypt, and the negative association of cell proliferation and unconjugated bile acids in the median compartment, do not seem to support the co-carcinogenic effect of deoxycholic acid.