AJP - Gastrointestinal and Liver Physiology, Vol 268, Issue 6 1051-G1059, Copyright © 1995 by American Physiological Society
Role of amidation in bile acid effect on DNA synthesis by regenerating mouse liver
E. R. Barbero, M. C. Herrera, M. J. Monte, M. A. Serrano and J. J. Marin
Department of Physiology, Faculty of Pharmacy, University of Salamanca, Spain.
Effect of bile acids on DNA synthesis by the regenerating liver was
investigated in mice in vivo after partial hepatectomy (PH). Radioactivity
incorporation into DNA after [14C]thymidine intraperitoneal administration
peaked at 48 h after PH. At this time a significant taurocholate-induced
dose-dependent reduction in DNA synthesis without changes in total liver
radioactivity content was found (half-maximal effect at approximately 0.1
mumol/g body wt). Effect of taurocholate (0.5 mumol/g body wt) was mimicked
by chocolate, ursodeoxycholate, deoxycholate, dehydrocholate,
tauroursodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate. In
contrast, chenodeoxycholate, glycocholate, glycochenodeoxycholate,
glycoursodeoxycholate, glycodeoxycholate, 5 beta-cholestane,
bromosulfophthalein, and free taurine lacked this effect. No relationship
between hydrophobic-hydrophilic balance and inhibitory effect was observed.
Analysis by high-performance liquid chromatography indicated that
inhibition of thymidine incorporation into DNA was not accompanied by an
accumulation of phosphorylated DNA precursors in the liver but rather by a
parallel increase in nucleotide catabolism. Bile acid-induced modifications
in DNA synthesis were observed in vivo even in the absence of changes in
toxicity tests, which suggests that the inhibitory effect shared by most
unconjugated and tauroconjugated bile acids but not by glycoconjugated bile
acids should be accounted for by mechanisms other than nonselective liver
cell injury.
