Tripodi A S, Feletti F, Molteni R, Germogli R
Institute of Pharmacology II, University of Pavia, Italy.
Arzneimittelforschung. 1993 Aug;43(8):897-903.
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.
通过5种不同的试验对一种新的胆汁酸——牛磺猪去氧胆酸（THDCA，Io，Praxis，CAS 2958-04-5）的致突变性进行了测定。艾姆斯试验（鼠伤寒沙门氏菌回复突变试验）和DNA损伤与修复试验（在酿酒酵母中）用于研究THDCA诱导的原核生物和真核生物中的遗传性突变（分别为每平皿100、200和400微克或每毫升100、200和400微克的剂量）。通过小鼠微核试验（口服研究中剂量为100、220和500毫克/千克，皮下研究中剂量为50、100和200毫克/千克）和人淋巴细胞细胞遗传学试验（THDCA剂量为50、100、220和500微克/毫升）研究体内和体外染色体畸变。最后，对经THDCA处理的小鼠（口服或皮下给药后）进行宿主介导试验，以测试其代谢产物对鼠伤寒沙门氏菌菌株的潜在诱变活性。这些研究获得的结果表明，THDCA不会诱导任何直接或代谢产物介导的促诱变、诱变或致断裂活性迹象。
