ENHANCEMENT OF CELL-PROLIFERATION AND PROSTAGLANDIN BIOSYNTHESIS BY 1,8-DIHYDROXYANTHRAQUINONE IN THE RAT LARGE-INTESTINE

The effects of 1,8-dihydroxyanthraquinone (DHAQ), a stimulant laxative named danthron, on cell kinetics and prostaglandin (PG) biosynthesis in the gastrointestinal tract were investigated in male 8-week-old F34 4 rats divided into three groups, each consisting of 10 animals, The a nimals in groups one, two and three were respectively given diets supp lemented with 0%, 0.1% and 0.2% DHAQ for 24 days, PGE(2) levels in the colorectal mucosa were significantly (P < 0.05 and 0.001) elevated af ter DHAQ treatment and showed some evidence of a dependence of DHAQ do se, consistent with the plasma PGE(2) levels, BrdU-labeling indices in the large intestinal epithelium were also significantly (P < 0.01) in creased, although the other portions of the gut such as the stomach an d small intestine were not significantly affected, Excretion of the ma in urinary metabolite of PGE (PGE-MUM) was significantly (P < 0.001 or 0.01) increased whereas the urinary PGE2 concentration and total PGE( 2) excretion were not changed, Thus the results of the present study c learly indicate enhancement of cell proliferation by DHAQ in the large intestine epithelia, correlated with increased PGE(2) levels in the l arge intestinal mucosa as well as the plasma, and possible support for the conclusion that quantitative analysis of urinary PGE-MUM, but not PGE(2) itself, offer a useful approach for biomonitoring exposure to such stimulant laxatives.