Mutagenicity Assessment Of A Benzopentathiepine Derivative In Ames Test

V. Bykov, head of Pharmacological Research Department, I. Sedykh, Ph.D. in Biology, Deputy President for general issues, A. Bykova, junior scientist LLC Innovative Pharmacology Research 634021, Russia, Tomsk, Elizarovikh str., 79/4 Е-mail:


Summary. Assessment of mutagenic properties of a new drug is an important part of its preclinical trials, because allows to study the drug’s ability to induce different mutations in fetal and somatic cells. An important aspect of mutagenicity assessment of a new drug is its structural similarity to the known mutagens. This structural similarity is analyzed with the aid of a large database of mutagenic properties of a wide variety of chemical compounds and with special computer programs. Experimental assessment of mutagenicity of new drug candidates requires the use of a battery of at least 2 tests, including an in vivo chromosomal damage test and a genetic mutation induction test, for which Ames test is usually used, which an accepted alternative to animal testing. On one hand, replacement of animals with less developed organisms is one of the 3R principles, on the other hand, using bacterial strains allows to screen compounds and quickly assess the potential genotoxicity of a compound. The obtained data can then be used to properly design subsequent toxicity tests. The present study assessed the ability of the test compound to induce mutations in S. typhimurium (ТА98, ТА100, ТА1535, ТА1537) and E. сoli (WP2 uvrA and WP2/pKM101) strains in six concentrations: 15,6; 31,2; 62,4; 125,0; 250,0 and 500,0 μg/ml. To assess potential genotoxicity of the test compound and its metabolites, we have performed testing with metabolic activation in the presence of rat liver S9 fraction (Aroclor-1254 inducer) and without it. The study has demonstrated the absence of mutagenic properties of the test compounds in all used bacterial strains, however, we can’t rule out possible genotoxicity after multiple administration.


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