In vitro and in vivo mutagenicity studies on taurohyodeoxycholic acid.
The mutagenicity of a new biliary acid, taurohyodeoxycholic acid (THDCA, Io, Praxis, CAS 2958-04-5), was assayed by using 5 different tests. The Ames test (reverse mutation assay on Salmonella typhimurium) and the DNA damage and repair test (in Saccharomyces cerevisiae) allowed to study the genetic THDCA-induced mutations in prokaryotes and eukaryotes (doses of 100, 200 and 400 micrograms/plate or 100, 200 and 400 micrograms/ml, respectively). In vivo and in vitro chromosomal aberrations were studied by using micronucleus test in mice (doses of 100, 220 and 500 mg/kg in oral study and 50, 100 and 200 mg/kg in subcutaneous study) and human lymphocytes cytogenetic test (doses of 50, 100, 220 and 500 micrograms/ml of THDCA). At last the host-mediated assay was performed on THDCA-treated mice (following oral or subcutaneous administration) in order to test the potential mutagenic activity of its metabolites on a S. typhimurium strain. The results obtained in these studies showed that THDCA did not induce any signs of promutagenic, mutagenic or clastogenic direct or metabolite-mediated activity.
Tripodi
A S
AS
Institute of Pharmacology II, University of Pavia, Italy.
Feletti
F
F
Molteni
R
R
Germogli
R
R
D000328:Adult; D000818:Animals; D002756:Cholagogues and Choleretics / Q000633:toxicity*; D002869:Chromosome Aberrations; D003434:Crossing Over, Genetic / Q000187:drug effects; D003470:Culture Media; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D005785:Gene Conversion / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D008875:Middle Aged; D008938:Mitosis / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013657:Taurodeoxycholic Acid / Q000031:analogs & derivatives* / Q000633:toxicity
D002756:Cholagogues and Choleretics; D003470:Culture Media; D009153:Mutagens; C083510:taurohyodeoxycholic acid; D013657:Taurodeoxycholic Acid