MUTAGENIC ACTIVITY OF TILORONE – ACTIVE PHARMACEUTICAL SUBSTANCE OF AMIXIN IN MICROTITER PLATE VARIANT OF AMES TEST

Abstract

Aim – to discover potential mutagenic activity of tilorone – active pharmaceutical substance of amixin. Methods. Mutagenic activity of tilorone was studied in the Ames test on Salmonella typhimurium ТА 98 (frame-shift mutations) and ТА 100 (Dot mutations – base pars change). Tilorone was examined in concentrations 5, 10, 50, 100 and 250 µg/ml. As standard mutagens, 2-nitrofluorene was used for Salmonella typhimurium TA 98 and sodium azide for Salmonella typhimurium TA 100 in tests without metabolic activation. In tests with metabolic activation, mutagen for both strains served as 2-aminoanthracene. The experiment was carried out with and without metabolic activation. In this work Muta-ChromoPlate kit (Biotoxicity, Canada) was used. Tilorone toxicity against salmonella strains was calculated at the same concentrations. Results. The obtained data show that in presence of standard mutagenic compounds amount of wells with mutated cells were 82–91%. At the same time in negative control this amount was not higher than 4.2%. In presence of tilorone amount of wells where mutated cells were detected, it was 4–16% – 3.3–13.0 times lower then the minimum value – 52%, which, according to protocol of micro titer plate test, is the evidence of mutagenic activity. In presence of all tilorone concentrations there is not any inhibition of bath growth of used Salmonella typhimurium strains. Conclusions. Tilorone in the range of used concentration did not posses any mutagenic activity or toxicity on S. typhimurium ТА 98 та ТА 100.