Importance of conjugation in bile acid-induced inhibition of
thymidine incorporation into dna by the regenerating mouse liver.
Barbero, Emilio R., Maria C. Herrera, Maria J. Monte, Maria A.
Serrano, and Jose J. G. Marin.
Departments of Physiology and Pharmacology and Biochemistry and
Molecular Biology, Faculty of Pharmacy, University of Salamanca,
37007-Salamanca, Spain
APStracts 2:0028G, 1995.
Effect of bile acids on DNA synthesis by the regenerating liver was
investigated on mice in vivo after partial hepatectomy (PH).
Radioactivity incorporation into DNA after [14C]thymidine i.p.
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 were found
(half-maximal effect at 0.1 mol/g body weight). Effect of
taurocholate (0.5 mol/g body weight) was mimicked by cholate,
ursodeoxycholate, deoxycholate, dehydrocholate,
tauroursodeoxycholate, taurochenodeoxycholate and taurodeoxycholate.
By contrast, chenodeoxycholate, glycocholate, glycochenodeoxycholate,
glycoursodeoxycholate, glycodeoxycholate, 5b-cholestane,
bromosulfophthalein and free taurine lacked this effect. No
relationship between hydrophobic/hydrophilic balance and inhibitory
effect was observed. Analysis by h.p.l.c. indicated that inhibition
of thymidine incorporation into DNA was not accompanied by an
accumulation of phosphorilated 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 non-selective liver cell injury.
Received 17 October 1994; accepted in final form 2 February 1995.
APS Manuscript Number G416-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 7 March 1995.